Abstract Metaplastic breast carcinoma is a rare histologic subtype of breast carcinoma, accounting for only 0.2 to 2% of all breast cancers. It is comprised of a heterogeneous histology involving mesenchymal and epithelial components. Metaplastic breast carcinoma usually harbors a triple-negative phenotype, but carries a worse prognosis compared to other breast cancer subtypes. Due to its unique histopathological and molecular characteristics, there has been limited data on the optimal management of metaplastic breast carcinoma. Moreover, the presence of a secondary breast neoplasm in the background of a prior ovarian carcinoma represents a diagnostic and therapeutic challenge. We report a case of a 55-year-old female with a previous history of serous ovarian carcinoma six years ago, who presented with an enlarging right breast mass. Digital mammography showed a right retro-areolar mass, 5.7 x 4.8 x 5.4 cm, BIRADS 4C. Initial biopsy done showed presence of atypical cells in a background of cystic change. The patient underwent modified radical mastectomy with incision biopsy and frozen section. Final histopathologic diagnosis was consistent with metaplastic breast carcinoma, mixed epithelial and mesenchymal type, Nottingham grade 2, with no lymphovascular invasion identified, pT2N0. Tumor was ER negative, PR negative, Her 2 neu negative, with Ki-67 of 10% on immunohistochemistry. She then underwent adjuvant treatment with 6 cycles of paclitaxel and carboplatin. Six years prior, the patient was likewise diagnosed with high-grade serous ovarian carcinoma. She had total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy with 6 cycles of Paclitaxel and Carboplatin was given. She had recurrence in the paraaortic lymph node after 3 years and underwent cytoreductive surgery with excision of nodule and hyperthermic intraperitoneal chemotherapy with cisplatin. Currently, the patient has no evidence of disease in the recent positron emission tomography scan, with normal serum CA-125 level. The current standard of care for metaplastic breast carcinoma follows that of triple-negative breast cancer. However, previous literature has shown that metaplastic breast carcinoma is more chemo-refractory compared to triple-negative breast cancer, with more response seen with taxane-based chemotherapy. Due to poor response rates to neoadjuvant chemotherapy, surgical management for early-stage disease is warranted. Targeting molecular alterations is necessary to improve the prognosis of this subtype. Genomic features of homologous recombination deficiency were also found to be more prevalent in metaplastic breast cancer, thus genomic testing is warranted, especially in the setting of a prior history of ovarian carcinoma. Citation Format: Raye Angeli Abella, Carlos Dy. METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-09.