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Mixed connective tissue disease (MCTD) is a unique disorder characterized by the presence of a high titer of anti-U1 ribonucloprotein antibody with overlapping features of various connective tissue disorders including systemic lupus erythematosus, scleroderma, and myositis. Severe renal or neurological involvement is unusual with this disorder. We describe a case of biopsy-confirmed severe sensorimotor axonal polyneuropathy in a middle-aged gentleman as his first presentation for MCTD.