Purpose: Defining the risk of neoplasia associated with gender-affirming hormone therapy (GAHT) is a priority for transgender medical research. The purposes of this article are to present a unique case of breast neoplasia in a transgender individual and to review the existing evidence base on GAHT as a potential risk for breast pathology. Methods: We present the case of a 76-year-old transgender patient who developed an estrogen receptor-positive mammary myofibroblastoma (MFB) after 13 months of treatment on feminizing hormones. To our knowledge, this is the first reported case of MFB occurring in a transgender individual. A literature review was conducted to identify all reported cases of breast neoplasia among transgender individuals receiving feminizing GAHT. Information was abstracted from each of the included cases to describe the existing body of literature and to compare published cases to the case reported in this study. Results: We identified a total of 19 malignant and 3 benign cases of breast neoplasia among transgender women. Ours is the first reported case of MFB in a transgender individual receiving feminizing hormones and the first reported case of breast neoplasia associated with GAHT administered via the estradiol patch. Conclusion: This case reinforces the need for additional reporting of breast neoplasia presenting in transgender individuals treated with feminizing hormones. The relationship between estrogen exposure and breast neoplasia in the transgender population remains poorly defined, and additional research is needed to define risks and inform clinical practice.