The anamnestic data and the clinical signs do not always leads to a correct diagnosis of progressive muscular dystrophy (PMD). The diagnosis is easier when hereditary data are present or when the longstanding course of the disease points to its irreversibility. The current laboratory tests, although useful for the evaluation of the muscular wasting, are not a safe aid in the differential diagnosis, since the results can be much alike either in PMD (especially in its onset or in cases with a subacute course) or in polymyositis and neuromyositis. Electromyography and muscle biopsy examination are the most reliable tests for the differential diagnosis. Electromyography shows, in PMD, low voltage and shorter action potentials, and a great incidence of polyphasic potentials. The histologic examination shows a marked variation in the caliber and degeneration of the muscle fibers and proliferation of the conective tissue, with no inflammatory infiltrate or full regeneration. These tests, however, are not sufficient by themselves for the differential diagnosis of all cases and must be carefully interpreted. Twenty-one cases which demanded a careful differential diagnosis are reported. In 17 cases (n.° 1 to 17) the diagnosis of PMD was supported by the anamnesis and the clinical signs; in all of them, however, a more accurate examination, aided by the electromyographic data and particularly by the histological findings, leads to a different diagnosis. In 2 cases (n.° 18 and 19) of Charcot-Marie-Tooth disease, the histopathologic examination suggested the diagnosis of PMD. In case 20 the clinical picture pointed to PMD and the electromyography showed a peripheral nerve lesion, while the histopathologic examination showed a compounl picture of PMD and neurogenic atrophy. In the last case (n.° 21) the clinical picture pointed to other disease, while the electromyography and the histopathologic examination gave safe data for the diagnosis of PMD. The author discusses in detail the difficulties for the differential diagnosis of the 21 cases here reported.