Detection of circulating tumor cells (CTCs) in human blood and lymph systems has the potential to aid clinical decision making in the treatment of cancer (Cristofanilli et al. New Engl J Med 351:781-791, 2004; Check Cap Today 19:1.76-1.86, 2005; Braun and Naume J Clin Oncol 8:1623-1626, 2005). The presence of CTCs may signify the onset of metastasis, indicate relapse, or may be used to monitor disease progression. We built and tested a photoacoustic flowmetry system for detecting circulating melanoma cells (CMCs) by exploiting the broadband absorption spectrum of melanin within CMCs. The device was tested on cultured melanoma cells in saline suspension, melanoma cells spiked in human blood, and in a Stage IV melanoma patient. The device showed a detection threshold of a single pigmented melanoma cell from culture. Results show the potential to assay blood samples from healthy and metastatic patients for the presence of cancerous melanoma providing a method for cancer screening.