Methotrexate is an effective but potentially toxic treatment for psoriasis. Well-known signs of methotrexate toxicity include bone marrow suppression and oral and gastrointestinal ulceration. Painful erosion of psoriatic plaques is a less common sign of methotrexate toxicity that may precede evidence of bone marrow suppression. We describe two patients in whom painful erosions of their psoriasis developed as the presenting sign of methotrexate toxicity and review the literature, emphasizing the risk factors associated with this manifestation.