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Irradiation of B78H1 murine amelanotic melanoma cells with 850 nm light emitted from a Ti:sapphire laser, operated in a pulsed mode at high fluence rates and in the presence of Ni(II)-octabutoxy-naphthalocyanine (NiNc), promoted a photothermally sensitised process leading to fast and irreversible cell death. This resulted in the ejection of a consistent mass of cytoplasmic material from the irradiated cells that was detected by scanning electron microscopy. The extensive chemical and mechanical damage was probably caused by the photoinduced generation of an acoustic shock wave. The efficiency of the photoprocess was modulated by intracellular concentration of NiNc and maximally by the formation of aggregated naphthalocyanine clusters in specific subcellular areas. Very similar results were obtained upon irradiation of NiNc-loaded C32 human amelanotic melanoma cells and transformed murine HT-1080 and HaCaT fibroblasts. From these results, photothermal sensitisation appears to be a general phenomenon and preliminary studies with mice bearing subcutaneously transplanted amelanotic melanomas, irradiated with 850 nm light 24 h after intravenous injection of NiNc, suggest that this approach has potential for the therapy of some types of skin tumours.