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To estimate the degree to which passive case detection underestimates the true incidence of cutaneous leishmaniasis in Guatemala, we compared data from the passive surveillance system of the Guatemalan Ministry of Health with a cross-sectional population-based survey of cutaneous leishmaniasis in Guatemala. Of the 2, 938 persons interviewed, 143 (5%) reported having had cutaneous leishmaniasis at some time in the past, 37 (1.3%) reported the onset of infection in the 12 months before the survey, 31 (1.1%) had active infections, and 16 (0.5%) had parasitologically confirmed infections. Calculated on the basis of these reports and the estimated population of the endemic area, the total number of new cases in the leishmaniasis-endemic area in the 12 months before the survey was ∼2, 574; during the same 12 month period, Ministry of Health data based on passive surveillance listed 64 cases of cutaneous leishmaniasis. In Guatemala, incidence estimates based on passive surveillance may underestimate the occurrence of cutaneous leishmaniasis by as much as a factor of 40.