Low-dose methotrexate has been proposed as therapy for patients with severely disabling psoriasis and psoriatic arthritis. However, it can be associated with severe toxicity, such as pancytopenia, characterized by anemia (hemoglobin level <
13 g/dL in men), thrombocytopenia (platelet count <
150 × 109/L), and neutropenia or agranulocytosis (neutrophil count <
1.5 × 109/L and 0.5 × 109/L, respectively). Here, we report a challenging clinical scenario characterized by pancytopenia and acute renal failure to inform clinicians about potential drug-drug interactions and subclinical renal insufficiency.