Three separate screening studies have tested the sensitivity and specificity of quantitative fluorescence image analysis for detecting bladder cancer. Nuclear intensity (NI) measurements of fluorescent dye-stained epithelial cells from voided urine and bladder washings were compared with routine Papanicolaou (Pap) cytology results, and findings were verified against pathological biopsy diagnoses. The NI cytology method detected the pathologically confirmed tumors earlier and with greater specificity than did conventional cytology. In the study of 140 clinically symptomatic patients in Oklahoma, the NI method detected 91.1% (31 of 34) of the pathologically confirmed grades 1 and 2 tumors and 100% of 18 grades 3 and 4 tumors. Pap cytology detected only 47% (16 of 34) of low-grade and 78% (14 of 18) of high-grade tumors. Comparable results were obtained in a study of symptomatic patients in Mississippi and the method has been employed in the screening of a high-risk occupationally exposed cohort in Georgia.