Multicentric reticulohistiocytosis is a very rare systemic disease that affects skin, mucosa and joints. We reported a case of a woman with multicentric reticulohistiocytosis who presented typical skin syndromes and arthralgia. Immunohistochemical analysis showed positive staining for S100 protein, which was reported negative in the majority of previously presented cases. Other immunohistochemical markers (CD68(+), CD1a(-), lagerin (-) and complete histologic and clinical picture were specific enough to make the definitive diagnosis of multicentric reticulohistiocytosis. The patient was administered prednisone just when arthritis appeared and we believe that this therapy protected her from the development of destructive arthritis. No autoimmune disease or internal malignancy was observed during 12-month follow up.