From his career lying in tatters on an Eindhoven training ground to the most coveted striker in Europe, Van Nistelrooy had a 2001/02 season of high personal achievement.
After a goal in the Charity Shield against Liverpool, his start to the season was slower than expected, perhaps a legacy of the much-criticised 4-5-1 formation Sir Alex Ferguson employed in United's stuttering start to the season.
Van Nistelrooy led United's charge back to the top with a run of eight goals in eight games and was also on fire in the Champions League where he finished top scorer in the competition with ten goals.
In Europe he played in that lone role and grew into a target man of real class, though it was in tandem with Ole Gunnar Solskjaer that the Dutchman really flew.
After such a long period out through injury he was always likely to run out of steam and so it proved as United faltered at the final hurdle. Though the club finished potless, Van Nistelrooy himself won the PFA Player of the Year Award.
He had eventually joined Manchester United for a British record fee of £19million in April 2001.
The transfer initially collapsed in the summer of 2000 when Van Nistelrooy broke down in training with a cruciate knee ligament injury just days after an £18.5million move to Old Trafford had hit the skids after United's medical team had found problems with his medial ligaments.
He returned to action in March 2001 and was immediately back among the goals, scoring twice to help PSV into the Dutch Cup final.
And United were forced to pay PSV an increased price of £19million for the player's services and the forward passed a thorough medical. He signed a five-year contract with the then Premiership champions.
He started his professional career with Den Bosch as a midfielder in 1993 after playing part-time for Nooit Gedacht and Magriet. Played only twice for Den Bosch in his first season, and it wasn't until 1997 that he hit form.
After netting 12 goals in 13 games, Heerenveen came calling and he made the switch, scoring 13 goals in 31 games in his first season.
Darren Ferguson, son of Sir Alex, alerted his father to the player's capabilities but PSV Eindhoven stole in to pay Heerenveen £3.4m on his 22nd birthday. Just four months later he made his debut for Holland against Germany.
He first international goal came in 1999 in a shock 2-1 defeat at the hands of Morocco.
In first season at PSV scored 31 goals in 34 matches - the highest in the league and second-highest in Europe and was voted Dutch Player of the Year by fellow professionals.
Van Nistelrooy was tracked by many of the top clubs due to his prolific record with PSV, in his second season at the club he had netted another 29 goals and was again the top scorer in Holland.