Photodynamic therapy (PDT) is regarded as a treatment option for basal cell carcinoma (BCC). The aim of this study is to investigate the efficacy of methylene blue (MB)-based PDT in patients suffering from nodular or ulcerative BCCs. This study is a prospective clinical trial with a 6-months follow-up. The study setting is at the Dermatology Clinic at NILES, Cairo University, Egypt. Seventeen patients complaining of nodular BCC (nBCC) and three patients complaining of ulcerative BCC (uBCC) were taken as samples. Methylene blue, the photosensitizer, was prepared in two different formulas: liposomal-loaded MB (LMB) was prepared and formulated in hydrogel (MB 0.2%) to be used topically alone for treating BCCs <2 cm in diameter or to be combined with intralesional injection (ILI) of free MB 2% aqueous solution for treating BCCs ≥2 cm in diameter. A session was performed every 2 weeks until complete response (CR) of the lesion or for a maximum of six sessions. Clinical assessments of clinical improvement, dermatological photography, monthly follow-up visits for 6 months, and skin biopsy after 3 months of follow-up to confirm the response, recurrence, or both in cases in which the clinical evaluation was ambiguous. Seventeen patients of the 20 completed the study, 11 patients achieved CR with very good cosmetic outcome, photosensitizer tolerance, and minimal reported side effects. MB is a cheap promising alternative photosensitizer for PDT of nBCC.