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Solar UV-exposure, particularly intensive short-time and recreational sun exposure, is considered to be the major etiologic factor for melanoma. But on the other hand 90% of all requisite vitamin D has to be formed in the skin through the action of the sun – a serious problem due to the fact that new scientific findings convincingly demonstrate vitamin D deficiency to be associated with a variety of severe diseases including various types of cancer (e.g. colon, prostate and breast cancer). According to recent reports sun exposure is associated with a relatively favorable prognosis and increased survival rate in various malignancies, including malignant melanoma. It has been speculated that these findings were related to UV exposure-induced relatively high serum levels of vitamin D which may lead to a more favorable course of melanoma. To prove this hypothesis the present study aimed to correlate the serum level of 25-hydroxyvitamin D (which represents the readily measurable ‘storage’ precursor form of vitamin D) with tumor thickness at time of diagnosis and course of disease in patients with melanoma. The study population consisted of 212 patients with histologically proven cutaneous melanomas of different stages: stage I (n = 50); stage II (n = 20); stage III (n = 20); stage IV (n = 122). Basal 25-hydroxyvitamin D levels were analyzed (DiaSorin LIAISON 25-OH Vitamin D-Assay) in those patients and compared with a control group (n = 80). Additionally, each participant was requested to fill out a questionnaire about the history of sun exposure. Interestingly, basal 25-hydroxyvitamin D levels were lower in melanoma patients as compared to the control group, although this difference was statistically not significant. Moreover, progression of malignant melanoma was associated with statistically significantly reduced 25-hydroxyvitamin D serum levels. In conclusion, our findings add to the growing body of evidence that 25-hydroxyvitamin D serum levels may be of importance for pathogenesis and progression of malignant melanoma.