Levels of eumelanin (EM) and pheomelanin (PM) of uveal melanoma cells have not been measured and compared with those of normal uveal melanocytes. EM and PM amounts in four immortal human uveal melanoma cell lines were measured by chemical degradation and microanalytical high-performance liquid chromatography and compared with those from 39 normal human uveal melanocyte cell lines reported earlier by us. Uveal melanoma cells had a very low EM/PM ratio (0.41), which was very significantly lower than that from normal melanocytes isolated both from eyes with light-colored irides (1.31) or dark-colored irides (7.32). The low EM/PM ratio was caused by a low level of EM in melanoma cells, which was only 1/8 and 1/31 of that in melanocytes from eyes with light-colored irides and dark-colored irides, respectively. The PM level in uveal melanoma cells was not statistically different from normal melanocytes from eyes with light-colored irides or dark-colored irides. The total quantity of EM and PM in uveal melanoma cells was significantly less than that in normal melanocytes. This difference was because of the low level of EM in uveal melanoma cells. The results of these studies indicate that the changes of melanin content in uveal melanoma cells mainly relate to the decrease of EM content. Low melanin and EM content may make melanoma cells more susceptible to mutagenic effects of ultraviolet radiation and oxidative stress, which may enhance the proliferation of melanoma cells and accelerate progression of melanoma.