In this work, Eakins depicts Dr. Agnew, standing at the edge of the operating arena, overseeing a procedure in which three doctors perform a mastectomy on a female patient. Behind them, a female nurse stands at attention, presumably waiting to assist in the operation. Rows of seated male medical students watch the surgery. The white clothes of the doctors, the sheets covering a part of the patient's body, as well as her pale skin stand in sharp contrast to the dark tones in which the students are painted.
This painting marks the second time Eakins took as his subject a doctor teaching and performing surgery in a medical school setting. Once again, the stark and often gritty Realism for which he is best known is present in this work, but when compared with his earlier painting The Gross Clinic (1875), we can see a different, perhaps even more mature, approach to the subject matter. The work is notably awash in light that helps to draw the viewer to the action of the surgery. A heightened element of drama is created by choice of surgery depicted. While Dr. Agnew was a specialist in this type of operation, a mastectomy was, to the general public, a shocking and scary surgery of which little was still known. The fact that it had a high fatality rate imbues the scene with a more serious tone. Eakins placed himself in the crowd of students (on the far right of the canvas), but the inclusion of a female nurse, modeled on the first nurse graduate from the university's program, is unique to this work. Dr. Agnew, familiar with the earlier painting of Dr. Gross, insisted on not being painted with blood on his hands, as surgeons were too often associated with butchers.
The University of Pennsylvania's School of Medicine students commissioned the portrait as a gift for Dr. D. Hayes Agnew, who was retiring at the end of the term. They had wanted a simple portrait of the doctor, but Eakins created a more elaborate scene at no extra fee. The successful reception of the work when it was unveiled at the school's graduation, which included a standing ovation, buoyed the artist's spirits, and set the stage for a successful, albeit not scandal-free, later career. Despite the rejection of the work from a Society of American Artists show, a slight which led to Eakins severing all ties with the organization, it was well-received when first shown to a large public at the Chicago World's Columbian Exhibition in 1893.