Venetoclax, a highly selective Bcl-2 inhibitor, is an orally bioavailable drug that has been approved as firstline therapy for chronic lymphocytic leukemia (CLL) in combination with obinutuzumab, as well as monotherapy in the setting of relapsed CLL. Although some of its lifethreatening side effects are well known, including tumor lysis syndrome and cytopenias, others less known side effects include skin reactions. Skin rash is commonly reported in literature, which is often mild and not lifethreatening. In this case report, the authors describe what is potentially the second case of venetoclax-induced vitiligo reported in literature. A 77-year-old man with CLL Rai stage II with cytogenetics showed 11 q23 deletion in 14% of cells, and 14q32 partial deletion in 9% of cells developed vitiligo in his extremities 2 years into treatment. A decision was made to continue venetoclax with close monitoring as the side effect was mild and not debilitating. The patient continued to do well. Although vitiligo is not associated with increased mortality risk, its development is associated with increased psychological stress. The mechanism by which vitiligo develops remains unclear. There may be an association between drug-induced vitiligo and improved cancer prognosis; however, larger studies need to be carried out to prove this hypothesis.