An evaluation of 3 different methods for malaria diagnosis was carried out in an urban area of low endemicity on the Pacific coast of Colombia. Samples were collected from 833 symptomatic patients at a malaria clinic and examined by the polymerase chain reaction (PCR), quantitative buffy coat (QBC; Becton Dickinson, Franklin Lakes, NJ) method, and the traditional thick blood smear. The prevalence of Plasmodium falciparum malaria was 5.88% by thick blood smear, 7.34% by the QBC method, and 21.87% by PCR. The agreement between microscopists was 99.5%. The agreement between the QBC method and thick blood smear was 96.13% (n = 745). Samples positive by PCR but negative by thick blood smear or conversely negative by PCR and positive by thick blood smear were usually of low-level parasitemias. All 3 methods showed agreement in 76.3% of the samples. Sixty-nine (18.8%) samples were positive by PCR but negative by the other 2 methods. Ten samples were positive by both the QBC method and thick blood smear but negative by PCR; most of them had low-level parasitemias. The use of malaria diagnostic methods for epidemiologic surveillance is discussed.