Skene’s (periurethral) gland adenocarcinoma is very rare, with only 7 cases reported in the literature. This is the first series of cases on this entity. We describe the histologic, immunohistochemical, and clinical findings of 4 patients with Skene’s gland adenocarcinoma retrieved from the Johns Hopkins Urologic Pathology Consult Service from 1984 to 2017. The average age at diagnosis of the 4 women was 74.5 years (range, 61 to 87 y). Tumors were treated by limited resections with negative margins. Tumor size ranged from 1.0 to 2.0 cm (mean, 1.5 cm). Average follow-up time was 40.7 months (range, 4 to 132 mo). Three of our cases were morphologically consistent with prostatic acinar adenocarcinoma with variable cribriform, fused, and poorly formed glands, analogous to Gleason score 4+4=8. Of these, one had mixed ductal features with neoplastic cells showing papillary carcinoma with columnar cytology. These 3 lesions were positive for PSA, P501S, NKX3.1, and AMACR. Focal goblet cells positive for CK20 and negative for prostatic markers were seen in one of these cases, suggesting intestinal differentiation (although negative for CDX2 and SATB2). A fourth case had glandular and papillary formations with pseudostratified columnar epithelium and mucin secretion, showing positivity for CK7, ER, and P16, and negativity for prostatic markers, suggesting serous differentiation (although negative for PAX8 and WT1). PIN4 cocktail confirmed the origin in preexisting paraurethral glands in 3 of the cases. All patients were alive and free of recurrence or metastatic disease at the time of last follow-up. Because of the rarity of Skene’s gland adenocarcinomas, there is no consensus regarding their treatment. Our findings demonstrate that Skene’s gland adenocarcinomas recapitulate morphologies and immunohistochemical markers seen in prostatic adenocarcinoma. However, it is unknown whether applying the same grading criteria for prostatic adenocarcinomas to Skene’s gland adenocarcinoma is valid given the small number of cases with variable treatment and limited follow-up.