<p>We report the case of an 82-year-old male acalabrutinib-treated patient with chronic lymphocytic leukemia (CLL) who was admitted to hospital because of a crural ulceration. Examination of a peripheral blood smear revealed 81% of the neutrophils as hypolobulated in addition to the leukemic lymphoma- and smudge cells. The nuclei of the abnormal neutrophils showed a markedly clumped chromatin and appeared as unilobular (round or oval) in 51%, bilobular in 13% and peanut- and band-shaped in 17%, respectively. A suspected diagnosis of a drug-induced acquired Pseudo-Pelger-Huet anomaly (PPHA) was made, because the morphological anomaly was not apparent in several blood smears prior to the initiation of acalabrutinib. Retrospectively, the presence of hypolobulation was first mentioned in a medical report two weeks after starting acalabrutinib. PPHA has been reported in a few patients with CLL, associated with different therapy regimens such as bendamustin- and fludarabine-containing chemotherapy protocols, venetoclax as well as the Bruton tyrosine kinase inhibitors ibrutinib and zanubrutinib. To our knowledge, an association of PPHA with acalabrutinib has not been previously described. The prevalence, the underlying pathomechanism as well as a potential clinical implication of this phenomenon have not been elucidated so far.</p>