A prospective 20-year (1988-2007) study in an STI unit in Spain investigating trends in Molluscum contagiosum infection included 12,424 patients. We found 339 Molluscum contagiosum infections (2.7% incidence) with a yearly distribution ranging from 0% to 6.8%. There was a three-fold increase from an incidence of 1.3% in the first decade (1988-1997) to 4.0% in the second (1998-2007) (P < 0.001).