Ginóbili made his professional début in the Argentine basketball league for the Andino Sport Club team of La Rioja from 1995-1996, and was traded to Estudiantes de Bahía Blanca the next year. He played with his hometown team until the Italian league attracted him, and in 1998 he moved to Europe, spending the 1998-1999 and 1999-2000 seasons with Basket Viola Reggio Calabria. Ginóbili then entered the 1999 NBA Draft and the San Antonio Spurs selected him late in the second round with the 57th overall pick.

However, he did not sign with the Spurs at this point in time. Instead, he returned to Italy to play for Kinder Bologna, which he helped win the 2001 Italian Championship, the 2001 and 2002 Italian Cups, and the 2001 Euroleague, where he was named Most Valuable Player (MVP). He was also named League MVP in 2000-01 and 2001-02, and made the Italian league's All-Star game three times during this period.

Ginóbili was drafted by the Spurs as the 57th pick in the 1999 NBA Draft, but it was not until after the 2002 FIBA World Championship in Indianapolis that Ginóbili joined the Spurs.

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