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Pleomorphic lobular carcinoma in situ (PLCIS) is a variant of LCIS with high grade morphologic features. However, the number of case series are limited, and the natural history and optimal clinical management are not well-defined. We report the largest breast core biopsy series of PLCIS which included 37 patients with PLCIS diagnosed on core biopsy. Upgrade rate to invasive carcinoma on excision was 60%, which was multifocal in 46%. Over one-half of our cohort had a family history of breast cancer.Pleomorphic lobular carcinoma in situ (PLCIS) is a variant of LCIS with high-grade morphologic features. The number of case series studying PLCIS is limited, and clinical management of patients with PLCIS is controversial. We report a breast core biopsy (BCBx) series of PLCIS.We reviewed 37 cases of PLCIS with or without microinvasion diagnosed by BCBx. PLCIS was defined as dyscohesive cells showing acinar expansion and loss of immunohistochemical membranous expression of e-cadherin or beta-catenin with nuclear pleomorphism with at least 2- to 3-fold variation in nuclear size, membrane irregularities, and variably prominent nucleoli. Clinical information and findings on excision were evaluated.Thirty-one (84%) patients presented with mammographic calcifications, 4 (11%) presented with ultrasound findings, 1 (3%) presented with magnetic resonance imaging enhancement, and 1 (3%) with combined imaging abnormality. The mean patient age was 62.3 years. Nineteen patients (51%) had a family history of breast cancer. Microinvasion was present on BCBx in 9 (24%) of the 37 patients. Excision, available in 34 patients, demonstrated invasive carcinoma in 24 (65%), which was multifocal in 11 (46%). Twenty-three patients with PLCIS without microinvasion on BCBx, and without known history of ipsilateral invasive cancer, underwent excision; 14 of these patients demonstrated invasive carcinoma, representing an upgrade to invasive carcinoma of 60%.We report the largest BCBx series of PLCIS and confirm its aggressive biology and frequent association with multifocal invasive lobular carcinoma, as well as frequent presentation in patients with a family history of breast cancer. Our results support excision to negative margins.