Abstract: Purpose: Polymyositis (PM) is an inflammatory muscle disease, which has more overlap with scleroderma than other connective tissue diseases. The aim of this study is to compare the clinical, paraclinical and therapeutic response of polymyositis with polymyositis-scleroderma overlap syndrome. Methods: During the past 10 years we had 16 overlap syndromes and 40 primary polymyositis. All patients were classified by the American college of Rheumatology classification criteria. Ninety-seven items were checked in every patient. Comparison was done with Chi square test. The Yates correction formula was applied when necessary. Results: The data seen in the polymyositis group versus the overlap group were as follow: Constitutional symptoms 68.9% /56.3% (P=0.54), acute onset of the disease 12.2% / 8.8% (P=1), proximal muscle weakness 64.2% / 68.8% (P=0.86). There was no significant difference for dysphagia, cardiac involvement, and articular manifestations. Raynaud's phenomenon 22.2% / 56.3% (P=0.04). Increased muscle enzymes (LDH, CPK, SGOT) and high ESR showed no significant difference between the two groups. Positive muscle biopsy 90% / 87.5% (P=0.72), myopathic pattern EMG 86% / 68.8% (P=0.31). The mean SGOT level in PM group was 21.5 before and 13.9 after the treatment (P=0.0003). In the overlap group it was 21.25 before and 12.5 after the treatment. (P=0.0004). Mean ESR in PM was 19.5 before and 15.3 after the treatment (P=0.03). In the overlap group it was 20 mm before and 14.16 mm after the treatment (P=0.03). The therapeutic response for proximal weakness showed no significant difference in the two groups (P>0.05). Conclusions: 1- Polymyositis and polymyositis-scleroderma overlap syndrome have the same clinical and paraclinical manifestations. 2- Raynaud's phenomenon is more common in the overlap syndrome. 3- The therapeutic response is the same in the two groups.