Solar ultraviolet radiation (UVR) is responsible for the development of many skin diseases, including malignant melanoma (MM). This study assessed the phototoxic effects of UVA, and UVB radiations on healthy and pathologic skin cells by evaluating the behavior of human keratinocytes (HaCaT) and MM cells (A375) at 24 h post-irradiation. The main results showed that UVA 10 J/cm2exerted no cytotoxicity on HaCaT and A375 cells, while UVB 0.5 J/cm2significantly reduced cell viability and confluence, induced cell shrinkage and rounding, generated nuclear and F-actin condensation, and induced apoptosis by modulating the expressions of Bax and Bcl-2. The association of UVA 10 J/cm2with UVB 0.5 J/cm2(UVA/UVB) induced the highest cytotoxicity in both cell lines (viability < 40%). However, the morphological changes were different—HaCaT cells showed signs of necrosis, while in A375 nuclear polarization and expulsion from the cells were observed, features that indicate enucleation. By unraveling the impact of different UVR treatments on the behavior of normal and cancer skin cells and describing enucleation as a novel process involved in the cytotoxicity of UVA/UVB irradiation, these findings bridge the gap between the current and the future status of research in the field.