A clinical syndrome of pathological left-handedness (PLH) is proposed to identify the pattern of correlative changes in lateral development associated with early brain injury in some manifest left-handers. This syndrome is believed to be caused by a hemispheric lesion that is predominantly left-sided (or bilateral asymmetric), which onsets before Age 6, and which encroaches upon the critical speech zones of the frontotemporal/frontoparietal cortex. The pattern of changes may include any or all of the following features: shifts in manual dominance, trophic changes in the extremities, transfer of hemispheric speech, and/or intrahemispheric reorganization of visuospatial cognitive functions. Although some of these correlates of PLH have long been known, they have not been recognized as an interrelated pattern of traits that constitute a clinical syndrome. Identification of these individuals, all manifest left-handers, will be shown to have implications for diagnosis/remediation and for models of recovery of function.