Here is presented, a rare case of disseminated protothecosis in a 10-year-old boy with combined immunodeficiency, hitherto unreported from India. Even though it is difficult to diagnose clinically, observation of the sporangiospores within the sporangium in culture gives the accurate laboratory identification of Prototheca spp. In this patient, failure to eradicate the infection with amphotericin B and recurrence with olecranon bursitis along with skin lesions and splenomegaly was observed. Disseminated protothecosis in a child with combined immunodeficiency and failure to eradicate the infection with amphotericin B is reported.