Pyrimethamine is used for the treatment of toxoplasmosis and the prophylaxis of malaria. Among the well-documented side effects are megaloblastic anemia, leukopenia, thrombopenia, rash, vomiting, and diarrhea. Hyperpigmentation is a very rare side effect. In some patients, associated HIV infection makes it difficult to distinguish the reasons for the etiology. We herein describe an HIV-negative patient who developed hyperpigmentation after pyrimethamine use.