To assess the association between unilateral carpal tunnel syndrome and space-occupying lesions, 128 patients have been reviewed. They were divided into bilateral, subclinical (unilateral signs and symptoms, and bilateral slowing in the median nerve conduction) and unilateral carpal tunnel syndrome. Space-occupying lesions were investigated on the basis of physical examination and wrist imaging using plain radiographs and ultrasonograms. Of 20 patients with unilateral carpal tunnel syndrome, space-occupying lesions were found in seven (occult ganglion in five and occult calcified mass in two). In contrast, none of 89 patients with bilateral carpal tunnel syndrome and 19 with subclinical carpal tunnel syndrome had space-occupying lesions. We conclude that careful examination and wrist imaging on suspicion of local pathology, especially a space-occupying lesion, are needed when the condition is unilateral and the aetiology is not clear from the history and on physical examination.