Multicentric reticulohistiocytosis (MR) is an uncommon disease with joint and cutaneous manifestations most commonly affecting women in middle age. The diagnosis must be confirmed by the histological evidence of typical mononuclear histiocytes and multinucleated giant cells. Many conditions have been described in association with MR, and the clinician should be aware that in many cases the disease is associated with malignancy. This eventuality must be accurately ruled out. If the typical nodular manifestations are missing at the onset, the arthritic complaints-usually localized but not confined to the interphalangeal joints-may be confused with those of more common rheumatic disorders. At this stage, a careful clinical and radiological evaluation may offer the key to the correct diagnosis. The natural course of the disease may develop into a severe, destructive arthropathy and disfiguring cutaneous lesions. In these cases an aggressive treatment with immunosuppressive drugs is strongly recommended. On the basis of recent reports, anti-tumor necrosis factor alpha agents and alendronate may also be added to the list of the drugs used in the treatment of this disease.