In most cases, advanced stages of melanoma are practically incurable due to high metastatic potential of tumor cells. Multiple observations support the idea that aberrations in the Wnt signaling pathway play a significant role in melanoma development and progression. Canonical Wnt signaling activation results in stabilization and accumulation of the major effector molecule called β-catenin. Mutations promoting β-catenin stabilization and, thereby, activation of canonical Wnt signaling pathway are frequently found in different cancers but rarely observed in melanomas. Nevertheless, β-catenin nuclear and cytoplasmic accumulation is the feature of many human melanoma cell lines and original tumors. That is why the aim of the investigation was to elucidate the relation between β-catenin intracellular localization and activity status of Wnt signaling pathway in human melanoma cell lines. Ten human melanoma cell lines were characterized on the basis of the following parameters: canonical Wnt ligand expression, intracellular -catenin localization and activity status of canonical Wnt signaling pathway. Here, it has been demonstrated that nuclear localization of β-catenin does not always correspond to active status of canonical Wnt signaling pathway. Moreover, in the majority of cell lines with nuclear β-catenin, canonical Wnt signaling cannot be activated by exogenous expression of an appropriate ligand. Human melanoma cell lines differ in activity of canonical Wnt signaling pathway as well as in mechanisms of its regulation. Therefore, pathway-targeted potential antineoplastic therapy requires the formation of a "molecular pattern of cancer" for localization of the defect in Wnt signaling cascade in each case.