First clinical report of Harlequin color change (HCC) phenomenon came in 1952 from Neligan and Strang. Since then, HCC has been described in a fairly broad number of clinical reports involving neonates, infants, children, and adult patients. We here present a small case series of HCC occurring in neonates, pointing out three of the different possible presentations (hemifacial, patchy scattered across the whole body, and hemiscrotal) of this phenomenon. A brief discussion and literature review encompassing epidemiology, clinical features, physiopathology, associated conditions, and differential diagnoses of HCC is then presented. In most cases, HCC represents a benign, idiopathic, and rapidly autoresolutive phenomenon, with no need for treatment. Some drugs (especially anesthetics and prostaglandin E) are thought to enhance HCC expression through their influence on the capillary tone in the peripheral vascular bed; this effect is anyway promptly reversible with drug withdrawal. Only in rare circumstances, HCC may act as a clue for serious central nervous system disorders (e.g., meningitis; hypothalamic, brain stem, or sympathetic nervous system lesions); anyway, in these rare occurrences HCC always represents an epiphenomenon of the disease, never acting as the sole sign of the underlying disorder.
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