OBJECTIVE Single, oval lesions greater than 5 mm in diameter lying inferior to the lateral putamen (infraputaminal lacunes [IPLs]) seen on CT or MR images are commonly reported as lacunar infarcts. To determine the clinical relevance and underlying pathology of IPLs, we evaluated the imaging appearances, clinical features, vascular risk factors, and histopathology in patients with IPLs. METHODS Consecutive MR scans were reviewed for the presence of IPLs. Serial patients seen in routine clinical practice with IPLs were also included. Vascular risk factors were obtained from a prescan questionnaire. Histology and microangiography were performed on postmortem material. A MEDLINE search for putaminal infarcts was performed to look for imaging lesions typical of IPLs. RESULTS Three of 100 serial MR scans had IPLs (3%). Nine other patients with in vivo (7) or postmortem (2) MR scans had IPLs. No neurological symptoms could be related to the IPLs. There were no differences in age, hypertension, diabetes, or presence of cortical enlarged perivascular spaces (EPVSs) between patients with and without IPLs. Unlike infarcts, IPLs were isointense with the cerebrospinal fluid on proton density MR sequences. Histological correlation of three MR scans showed IPLs to be a single large EPVS, situated lateral to the anterior commissure. IPLs were located at a point where multiple lenticulostriates turn sharply dorsally. An IPL was the probable cause of the apparent infarct in six publications from peer-reviewed literature that linked different clinical signs to putaminal infarct. CONCLUSIONS IPLs are EPVSs that can be differentiated from infarcts on proton density MR images.