The seven-time Tour de France winner apparently touched the wheel of the rider in front of him as the main pack went around a hairpin curve. He hit the pavement on his left side the opposite side from his crash in March when he broke his collarbone.
Armstrong got right back up, changed his rear wheel, and rejoined the main pack.
Italian rider Mauro Da Dalto also went down with Armstrong, race radio reported.
Armstrong is 12th overall in the Giro, 12 minutes, 17 seconds behind race leader Denis Menchov. The race ends Sunday.
After the March 23 crash in Spain, a stainless steel plate and 12 screws were inserted into Armstrongs right collarbone.
Fridays 102-mile leg began in Avellino and finishes with a climb up the Mount Vesuvius volcano. Armstrongs fall came at about the 47-mile mark.