Hamburg's unique record of being Bundesliga ever-presents will come under serious threat in Saturday's conclusion to the season.
Elsewhere, Bayer Leverkusen, Wolfsburg and Borussia Monchengladbach will fight for the last remaining UEFA Champions League qualification slot as Robert Lewandowski and Mario Mandzukic compete to finish top of the scoring charts.
While each of their fellow 15 co-founders have succumbed to relegation since the Bundesliga's 1963 inception – maiden champions Cologne being the last in 1998 – Hamburg have never gone into the final day sweating over their status.
But Mirko Slomka's side sit third bottom, just one point above Nuremburg with Eintracht Braunschweig a further point back.
One of the trio will go into a play-off for a place in the 2014-15 Bundesliga – almost certainly against Greuther Furth – while demotion will befall the other two.
Hamburg have lost their last four games, their last eight away, and have not kept a clean sheet in 12 matches. However, Slomka is optimistic he can record his 100th Bundesliga victory as a coach when he takes his team to UEFA Europa League-chasing Mainz.
Johan Djourou and key forward Pierre-Michel Lasogga have recovered from injuries, while Hamburg have lost just one of their seven trips to Mainz in the Bundesliga.
Nuremberg must attempt to end a run of six straight defeats by winning at third-placed Schalke for the first time in 21 years, while Braunschweig – winless and goalless in four outings – visit free-scoring Hoffenheim.
A number of people within German football have expressed their desire to see Hamburg, founded in 1887 and known as 'The Dinosaur', survive.
"I hope they can avoid relegation," Pep Guardiola said of the 1982-83 European Cup winners. "A club with so much history belongs in the Bundesliga."
Guardiola's runaway champions Bayern Munich, who beat Hamburg 4-1 last time out, are at home to fourth-bottom Stuttgart.
Thomas Muller could make his 200th league appearance – and potentially his last for Bayern – while Mandzukic will hope to boost his chances of finishing as the competition's leading marksman.
The Croatia striker is level on 18 goals with Lewandowski, whom he will compete with for a place in the Bayern attack next season.
Lewandowski's last league game for Dortmund is away to mid-table Hertha Berlin.
Bayer Leverkusen are one point above Wolfsburg and two clear of Borussia Monchengladbach in the race for the fourth and final Champions League berth.
Leverkusen are at home to Werder Bremen, while Wolfsburg host Monchengladbach.
Augsburg will pip Mainz to the final Europa League spot if they win at home to Eintracht Frankfurt and Hamburg avoid defeat at the Coface Arena.
Finally, Hannover and Freiburg meet in a match of little importance.
|Coach: T. Tuchel|
for E. Soto 83'
for Ja-Cheol Koo 83'
for Y. Malli 90+1'
|Gaya: Six finals left for Valencia|
|Muller wary of Porto counter-attacks|
|Bartomeu plays down Pogba link|
|Verratti hails ´essential´ Ibrahimovic|
|Zidane backs PSG to upset Barca|
|America v Montreal Impact: Klopas unfazed by host´s form|
|Vlaar open to Villa stay|
|Shepherd urges fans not to boycott Newcastle|
|Maritimo 1 Nacional 1: Tiquinho ensures derby finishes all square|
|Fiorentina 0 Verona 1: Diamanti and Neto pay the penalty|
|Elche 1 Real Sociedad 0: Bergara gifts win to hosts|
|Van Persie returns in Under-21 game|
|Turkish Super Lig Review: Galatasaray slip sees Fenerbahce go top|
|Russian Premier League Review: Arsenal Tula and Rostov maintain survival bids|
|Frontzeck named as Korkut´s replacement at Hannover|
|Lopetegui wary of Bayern backlash|
|Pastore plays down Cantona´s world best tag|
|PSG absences no excuse for failure - Blanc|
|Suarez sad to see Gerrard leaving Liverpool|
|Cleber injury adds to Hamburg woes|
|Northern Ireland free to play Romania at Windsor Park|
|Juve sweating on Vidal availability|
|Monaco v Juventus: Evra ready to take control|
|Striking concerns for Chelsea after Drogba injury|
|PSG and Chelsea have bid for Dybala, claims agent|
|Pogba can leave Juve for ´right offer´|
|Bendtner dropped after arriving late for training|
|Messi achievement unrepeatable, says Luis Enrique|
|Football League Preview: Preston and MK Dons battling to join Bristol City|
|Real Madrid v Atletico Madrid: Ancelotti optimistic amid injury concerns|
|Iniesta declared fit for PSG second leg|
|Bale remains a doubt for Atletico clash|
|Schweinsteiger set to face Porto, Ribery to miss out|
|No broken cheekbone for Silva|
|Final appearance can remove negativity at Villa - Fox|
|Bale selected in Football League Team of the Decade|
|PSV director: United and PSG want Depay|
|Korkut sacked by relegation-threatened Hannover|
|Sherwood: Pressure all on Arsenal|
|Newcastle in a ´dangerous moment´ - Colback|
|Kovac hopes to have Modric fit for Euro qualifier|
|Copa Libertadores Preview: Cruzeiro boss Oliveira does not fear sack|
|MLS Review: Revs extend unbeaten run, Timbers stun City|
|Fournier proud and disappointed|
|Shaw ready to make an impact|
|Hazard among best three in the world - Mourinho|
|Carver: Newcastle are in relegation battle|
|CAF Champions League Review: Setif get two away goals, Al Ahly denied late on|
|Inzaghi praises Milan derby officials|
|La Liga Review: Granada frustrate Sevilla, Villarreal´s woes continue|
|Inter should have had a penalty, Mancini fumes|
|Ligue 1 Review: Lyon return top after derby draw|
|Inter 0 Milan 0: Disappointing derby ends in stalemate|
|Primeira Liga Review: Sporting made to battle, Penafiel running out of time|
|Balotelli targets officials in latest social media outburst|
|Bundesliga Review: Werder Bremen edge Nordderby, De Bruyne rescues Wolfsburg|
|Serie A Review: Napoli close on stumbling Roma|
|Pochettino congratulates 30-goal Kane|
|Rodgers questions Liverpool´s mental strength|
|Carver counting on experience after latest defeat|
|Sherwood marvels at Grealish potential|
|Eredivisie Review: Dordrecht relegated as Go Ahead Eagles stun Feyenoord|
|Newcastle United 1 Tottenham 3: Losing streak continues amid fan boycott|
|Kouyate elbow on Silva accidental - Allardyce|
|Aston Villa 2 Liverpool 1: Delph ends Gerrard´s hopes of dream farewell|
|Pellegrini hails City response to derby defeat|
|Silva back home after Kouyate elbow|
|Manchester City 2 West Ham 0: Silva injury sours routine win|
|Bayern Munich v Porto: Neuer rallies Germans for uphill battle|
|Barcelona v Paris Saint-Germain: Marquinhos keeps the faith ahead of Camp Nou test|
|Fer closes in on QPR return|
|Crouch set for surgery|
|Dortmund confirm Tuchel as Klopp replacement|
|Adams leaves relegation-threatened Tranmere|
|Real still unsure over Modric injury|
|Tevez rubbishes Juve exit talk|
|Moyes: I had to fight to keep Rooney at United|
|Perth Glory 3 Melbourne City 1: Maclaren treble the difference|
|Dyche: Burnley are too honest|
|Illarramendi eager for Real stay|
|Hazard issues Chelsea warning|
|MLS Review: Injury-time winner buoys Galaxy, Martins shows class for Sounders|
|Pastore talents ´unpredictable´ - Blanc|
|Liverpool much bigger than City - Rodgers|
|AFC Champions League Preview: Evergrande look to progress|
|Clarke expects distraught Federici to bounce back|
|Toure is City´s scapegoat - agent|
|Allegri praises high-flying Juve|
|Athletic Bilbao 4 Getafe 0: Hosts end winless run|