Background: Erythema multiforme is an immune mediated cutaneous eruption. It is most frequently associated with infectious disease and drug intake. However, it can be associated with malignant disease such as leukemia. Aim: Report new case of erythema multiforme associated to an acute monoytic leukemia. Materials and methods: We report the case of a women presenting with erythema multiforme leading to the diagnosis of acute monocytic leukemia. Results: A 54-year old woman was admitted in our internal medicine department for an extensive skin rash on the face and the limbs which had been evolving for 15 days prior to admission associated with asthenia and important weight loss. Clinical examination showed an erythematous; purpurish infiltrated non purpuric nodules and papules having symmetrical distribution on the face, neck and the four limbs. Blood cell count revealed non regenerative macrocytic anemia (hemoglobin: 8.9 g/dl with mean corpuscular volume at 102 fl), thrombocytopenia (platelet: 44000/mm3) and leukocytosis at 13200/mm3 with monocyte count at 7190/mm3. A biopsy of nodular cutaneous lesions showed lesions evoking erythema multiforme. A bone marrow biopsy was performed revealing a monoblast infiltration of the marrow estimated at 20%. The diagnosis of monocytic leukemia, M5 in the French-American- British classification (FAB) was retained. Conclusion: Although erythema multiforme can be attributed to various conditions such as drug intake and environmental xenobiotic which became a cause of concern in developing countries, it still warrants a thorough investigation that can lead to a severe disease diagnosis such as monocytic leukemia.