Versican is a large chondroitin sulfate proteoglycan produced by human melanoma cell lines and malignant melanocytic lesions. In the present work, we have analyzed the expression of versican spliced variants V0, V1, V2 and V3 in human melanoma cell lines at several differentiation degrees. The isoform expression pattern depends on the degree of cell differentiation. Differentiated cell lines do not produce any of the versican isoforms as analyzed by Western blot, Northern blot and RT-PCR. All cell lines with an early or intermediate degree of differentiation (AX3, SK-mel-37, Rider, SK-mel-1.36-1–5 and SK-mel-3.44) expressed V0 and V1 transcripts, whereas V2 and V3 expression was shown only by the undifferentiated cell lines SK-mel-1.36-1–5 and Rider. Furthermore, we have analyzed the expression of versican isoforms in SK-mel-3.44 and SK-mel-1.36-1–5 cells induced to differentiate by TPA treatment. The expression of the large V0, V1 and V2 isoforms practically disappears in differentiated cells, whereas V3 remains detectable by RT-PCR analysis.