A 65-year-old woman presented with cutaneous, pruritic papules of the upper part of her chest. Histologic findings and culture of a biopsy specimen confirmed that these papules were caused by an infection with Prototheca wickerhamii, an achloric alga that rarely infects humans. Natural killer cell activity in this patient was significantly depressed before initiation of therapy. Reevaluation following successful treatment with oral tetracycline hydrochloride and topical amphotericin B cream revealed an improvement in natural killer cell activity. This patient is presented to demonstrate a rare clinical presentation of protothecosis; to document that cutaneous protothecosis can be successfully treated without the risk of toxic side effects associated with systemic antifungal agents; and to illustrate that although most patients with cutaneous protothecosis are immunosuppressed, infection with this alga appears to be at least partially responsible for the immunosuppression.