Context: The search for innovative therapeutic approaches is gaining more interest in clinical oncology.Objective: In the present investigation we reported the chemical profile and the photo-induced cytotoxic activity of two endemic Calabrian Citrus species (Rutaceae): Citrus bergamia Risso & Poit. and Citrus medica L. cv. Diamante.Materials and methods: Essential oils were obtained by hydrodistillation and analyzed by GC and GC/MS. In order to evaluate the cytotoxic activity two melanoma models, such as amelanotic melanoma C32 and malignant melanoma A375, were used.Results: The essential oil of C. bergamia was characterized by limonene, linalyl acetate, γ-terpinene, linalool and β-pinene as major components. The most abundant compounds of C. medica cv. Diamante oil were limonene, γ-terpinene, citral, geranial, β-pinene and α-pinene. Two coumarins, bergapten and citropten, were also identified in C. bergamia and C. medica cv. Diamante, respectively and tested for biological activity. Both C. bergamia and C. medica cv. Diamante oils exhibited a selective interesting activity against the A375 cell line with IC50 values of 79.3 and 89.1 µg/mL, respectively, after 100 min exposure to UV irradiation. The strong antiproliferative activity demonstrated with bergapten (IC50 value of 71.3 µg/mL after 20 min of irradiation) was not found with citropten.Discussion and conclusion: Our study suggested that UV irradiation is effective in activating essential oils and in particular bergapten. This phototoxicity may be considered as a treatment option in some cases of lentigo maligna or lentigo maligna melanoma.