Among tumors of the eye, uveal melanoma is the most common. When metastases occur, mortality approaches 90 %. In studies on a particular uveal melanoma cell line, Mel-290, we discovered what appear to be abnormal steady state cellular levels of sodium and potassium. Measured by atomic absorption spectrometry, the ratio of sodium concentration to potassium concentration in Mel-290 cells was 0.57 compared to 0.1 in a different melanoma cell, OCM-3, and 0.15 in pig ciliary epithelium. Assuming the sum of Na + K concentration totals ~140 mM, Mel-290 cells have resting sodium concentration of approx. 50 mM which is considerably higher than the concentration expected in normal cells. Western blot studies were conducted to examine the Na,K-ATPase alpha 1 which is the most common isoform of Na,K-ATPase in human cells. Mel-290 displayed a lower abundance of Na,K-ATPase alpha 1 subunit protein compared to OCM-3. Differences in Na,K-ATPase alpha subunit phosphorylation also were observed. In contrast to Na,K-ATPase alpha 1, H/K-ATPase beta subunit and H-ATPase (v-ATPase) beta subunit were found by Western blot to be higher in Mel-290 compared to OCM-3. A high sodium:potassium ratio was detected in two other melanoma cell types, suggesting the possible existence of a high sodium sub-group of melanomas. More studies are required to determine whether the high-sodium phenotype is linked to a particular pattern of ATPase expression or regulation. It is noteworthy that high cytoplasmic sodium has been reported in certain liver, breast and brain tumors.