The starry sky pattern is a distinctive histologic feature wherein a rapidly proliferating hematolymphoid neoplasm contains scattered histiocytes with abundant pale cytoplasm in a background of monomorphic neoplastic cells. The cytoplasm of these histiocytes typically contains cellular remnants, also known as tingible bodies, incorporated through active phagocytosis. Although common and widely recognized, relatively little is known about the pathophysiological underpinnings of the starry sky pattern. Its resemblance to a similar pattern seen in the germinal centers of secondary follicles suggests a possible starting point for understanding the molecular basis of the starry sky pattern and potential routes for its exploitation for therapeutic purposes. In this review, we discuss the historical, pathophysiological, and clinical implications of the starry sky pattern.