Factors associated with left-handedness were examined in a large sample of adults who suffered with epileptic seizures (n = 446) in an attempt to delineate the concept of pathological left-handedness. Three main pathological factors were found associated with left-handedness: (i) right-hemiparesis of early onset; (ii) cognitive deficit; (iii) evidence of left-hemisphere disease on clinical examination. Familial sinistrality was also associated with left-handedness, independently of the above-mentioned pathological factors. Results support a clear-cut distinction between normal and pathological left-handedness. This distinction seems presently important for the evaluation of the great number of anomalies proposed to be associated with left-handedness.