Porphyrin (Por) dyes are considered photoactive entities with potential properties to be applied as photosensitizers (PS) in cancer Photodynamic Therapy (PDT). The use of suitable units, like pyridinium ones, is an important strategy to add peripheral and non-peripheral positive charges in the Por structure, and in that way develop effective cationic PSs for melanoma treatments. In this context, free-base porphyrins bearing thiopyridinium (1) or methoxypyridinium (2) units were studied on melanoma cells, and their PDT effectiveness was studied and compared. The different charge positions of the cationic peripheral units on the Por macrocycle contribute differently to their PDT behavior. The obtained results demonstrate high in vitro PDT efficacy for both PSs. For the highest PS concentration tested (20 [Formula: see text]M) the photocytotoxicity reaches the detection limit of the MTT assay upon 201 seconds of blue light irradiation ([Formula: see text] = 405 ± 20 nm) at an irradiance of 24.9 mW/cm², which corresponds to a light dose of 5 J/cm². Interestingly, under the same experimental conditions, cationic Por 1 shows very interesting PDT results at lower concentrations of 1 to 10 [Formula: see text]M.