The Lycaonian city of Lystra appears six times in the Bible (Acts 14:6, 8, 21; 16:1, 2; 2 Tim 3:11). Located approximately twenty-five miles south by south-west of Iconium, this city was originally a Roman colony, colonized by Roman army veterans, under Augustus Caesar in 26 B.C. The colony was founded on the route called Via Sebaste to provide protection from hostile mountain tribes.

Inscriptions dated to the era before Paul's arrival, as well as the Roman poet Ovid's Metamorphoses (8.616-724), describe the gods Zeus and Hermes wandering about the city as unwelcomed, unadorned visitors. After Paul healed a crippled man (Acts 14:8-10) so that he could leap (vs. 10) for all to see, Lystrans (connecting the myth with the reality of Paul's miracle) wrongly concluded that Paul (the chief speaker) and Barnabas were actually Hermes (the messenger god) and Zeus respectively, and brought sacrificial bulls and garlands to worship them. Led by the priest of the temple of Zeus outside the city (14:13), the residents cried out in Lycaonian, "The gods have become like men and have come down to us" (Acts 14:11)! After Paul refused such idolatry (14:14-18) the fickle crowd degenerated, at the instigation of unbelieving Jews (14:19), into an angry, violent mob. In a public riot (cf. 2 Tim 3:11), they stoned Paul, dragged him outside the city, and left him for dead (Acts 14:19). Nonetheless, Paul later returned with Silas on his second missionary journey, recruiting Timothy, who was highly regarded by the brethren in Iconium and Lystra, and whose father was Greek (Acts 15:40-16:4). Paul would later write the two epistles to Timothy, his son in the faith (1 Tim 1:2).