A 72-year-old woman with a history of diffuse large B cell lymphoma and recent recurrence visited our department complaining of several painful edematous nodules with blisters on her face. She had iteratively developed cutaneous eruptions after every treatment with granulocyte colony-stimulating factor (G-CSF) for neutropenia, and each time the eruption improved after the cessation of the G-CSF treatment. The blisters became crusty and the skin lesions slightly improved, but on the 24th hospital day, the eruption formed painful erythematous nodules with erosion, and the patient also developed a high fever of up to 38°C. A biopsy specimen showed a dermal infiltrate of increased and enlarged plump histiocytes, some of which indicated karyomitosis with a small number of lymphocytes. No increase in the number of eosinophils or neutrophils was noted. These eruptions lasted for 15 days and disappeared with the recovery of the peripheral blood count and attendant cessation of G-CSF. We diagnosed this case as G-CSF-induced granulomatous dermatitis with enlarged histiocytes. Several cases with maculopapular rash and dermal inflammatory infiltrate composed of interstitially arranged large histiocytes have been reported. However, to the best of our knowledge, this is the first case report of G-CSF-induced granulomatous dermatitis with enlarged histiocytes clinically manifesting as painful edematous nodules with a high fever, similar to Sweet's syndrome. We speculated that the infiltrating cells were not neutrophils but histiocytes, presumably because of agranulocytosis.