Armstrong has yet to win a stage in the Tour this year, but history is definitely in the Texan's favour for the 55.5km solo race against the clock starting and finishing in the grimy industrial city of St Etienne.
Since 1999, Armstrong has won all but one of the race's final time trials - the exception being in the Tour where he was at his most vulnerable, 2003 - and after yesterday's stage he made it plain, despite retirement being just 48 hours away, that he was far from demob happy.
"It's a big day, I'll give it everything I have," said Armstrong, who has always insisted that the yellow jersey should show why he is leading in the last time trial. "I'm just five hours away from finishing my career, but I'm not throwing a retirement party just yet," he concluded.
Together with the remainder of the favourites, in anticipation of the time trial Armstrong held his fire on yesterday's stage - at 153km the shortest this year but, with five classified climbs through the little-known Haute-Loire region on the menu, no cakewalk at all.
The veteran climber Giuseppe Guerini of Italy was one of the few riders present on this year's Tour when it last visited the region 10 years ago, and he used that knowledge of the finish at Puy-en-Velay to full effect, pulling off an unexpected but well-calculated stage win. Knowing he was the weakest of a quartet of breakaways for a final sprint, Guerini intelligently hung back, so that if he attacked before the line - as proved to be the case - the other three would not have time to react.
Guerini's time-honoured strategy paid off to perfection, with the 35-year-old gaining an advantage of 10 seconds over his closest pursuer, Sandy Casar of France, by the time he crossed the line. His hand-waving and huge grin were understandable: with Armstrong threatening to go on the rampage today, and tomorrow almost certain to end in a bunch sprint, this was the last chance for a breakaway to go clear.
"It was a question of now or never," said Guerini, who last took a Tour stage win in 1999 on Alpe d'Huez.
For Armstrong, securing his 22nd and last stage victory today, as well as a seventh Tour victory tomorrow, should prove a much safer bet.
Looking ahead to life after cycling, Armstrong remarked: "I don't have a script for it. I'm 34 years old and I'm retired. So that is a little daunting. There's a lot of life to live.
"Of course I am a little nervous about what fills your day. I will miss day-in, day-out competition. The reality is that I don't ever have to work again, which is a nice reality. But that's not my character. My character is to work and to be goal-oriented."
Alasdair Fotheringham writes for 'Cycling Weekly'
Issoire to Le Puy-en-Velay, 153km, 95 miles: 1 G Guerini (It) T-Mobile 3hr 33min 04sec; 2 S Casar (Fr) Française des Jeux +10sec; 3 F Pellizotti (It) Liquigas +10s; 4 O Pereiro (Sp) Phonak +12s; 5 S Commesso (It) Lampre-Caffita +2:43; 6 K-A Arvesen (Nor) CSC +2:48; 7 N Portal (Fr) AG2R; 8 B Grabsch (Ger) Phonak; 9 S Chavanel (Fr) Cofidis; 10 P Weening (Neth) Rabobank +3:50.
Overall: 1 L Armstrong (US) Discovery Channel 81hr 22min 19sec; 2 I Basso (It) CSC +2:46; 3 M Rasmussen (Den) Rabobank +3:46; 4 J Ullrich (Ger) T-Mobile +5:58; 5 F Mancebo (Sp) Illes Balears +7:08; 6 L Leipheimer (US) Gerolsteiner +8:12; 7 C Evans (Aus) Davitamon-Lotto +9:49; 8 A Vinokourov (Kaz) T-Mobile +10:11; 9 F Landis (US) Phonak +10:42; 10 Pereiro +12:39.
Points: 1 T Hushovd (Nor) Crédit Agricole 175; 2 S O'Grady (Aus) Cofidis 160; 3 R McEwen (Aus) Davitamon-Lotto 154; 4 Pereiro 118; 5 A Davis (Aus) Liberty Seguros 110.
Mountains: 1 Rasmussen 185pts; 2 Pereiro 155; 3 C Moreau (Fr) Crédit Agricole 92; 4 Armstrong 92; 5 M Boogerd (Neth) Rabobank 90.
U-25: 1 Y Popovych (Ukr) D Channel 81hr 38min 12sec; 2 A Kashechkin (Kaz) +7:47. 3 A Contador (Sp) L Seguros +41:20.