Cyclin4/6-dependent kinase inhibitors (CDKIs) plus hormonotherapy currently represent the standard golden treatment for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2-negative (her-2-) advanced breast carcinoma. Among CDKIs, abemaciclib is the most active. No data on the use of abemaciclib in patients with end-stage renal disease (ESRD) exist in the medical literature. Two women with ER+, her-2- metastatic breast cancer received standard hormonal therapy plus abemaciclib 100 mg b.i.d. under strict monitoring for toxicity. Although ESRD exposes patients to a higher risk of toxicity from antineoplastic agents, no unexpected or severe toxicity was recorded in both patients after 9 and 12 months of therapy. In 1 patient, grade 2 diarrhea started after 7 days of therapy and disappeared or was significantly reduced after using loperamide and dietary modifications. Both patients complained of grade 1 asthenia. Hematological parameters were in line with expected toxicity. No cardiovascular or hepatic side effects were observed. This report of two women with metastatic breast cancer suggests the potentially safe use of abemaciclib in ESRD, which should be confirmed in more extensive real-life studies.