Objectives: Endorectal endoscopic ultrasound (ERUS) allows highly detailed assessment of the rectal wall layers and visualization of the extraluminal structures. Herein, we study the utility of ERUS fine-needle aspiration (FNA) to evaluate perirectal lesions. Study Design: Forty-nine ERUS-FNAs were retrieved from the cytopathology archives of The Johns Hopkins Hospital. The cytology slides, corresponding histology, immunohistochemistry when available, and clinical data were reviewed. Results: The aspirated material showed malignant (n = 24), benign (n = 19), atypical (n = 3), carcinoid tumor (n = 1), and nondiagnostic conditions (n = 2). The past medical history of 36 cases was significant for carcinomas. The primary site of the tumors included colorectal, urinary bladder, prostate, pancreas, gallbladder, ovary, and female lower genital tract. Statistical analysis for endoscopic ultrasonography FNA showed 87% sensitivity, 100% specificity, diagnostic accuracy of 90%, and a positive predictive value of 100% and a negative predictive value of 77%. Conclusion: ERUS-FNA can be utilized for: (1) accurate staging of colorectal adenocarcinomas by evaluation of nodal metastasis, depth of transmural tumor invasion and local tumor spread to perirectal fat, (2) prevention of aggressive surgical intervention in benign conditions, (3) providing diagnostic material for ancillary studies, and (4) evaluation of perirectal lesions with a more accurate method by combining imaging and histology.