An incorrect diagnosis is made at the initial examination in up to 25% of patients with testicular tumors and may result in delay in treatment or a suboptimal surgical approach (scrotal incision) for exploration. Epididymitis or epididymoorchitis is the most common misdiagnosis in patients with testis cancer. Early epididymitis should reveal an enlarged, tender epididymis that is clearly separable from the testis. In advanced stages, the inflammation may spread to the testis and result in an enlarged, tender, and indurated testis and epididymis. A history of acute onset of symptoms including fever, urethral discharge, and irritative voiding symptoms may make the diagnosis of epididymitis more likely. Ultrasonography may identify the enlarged epididymis as the cause of the scrotal mass.

Hydrocele is the second most common misdiagnosis. Transillumination of the scrotum may readily distinguish between a translucent, fluid-filled hydrocele and a solid testicular tumor. Since 5-10% of testicular tumors may be associated with hydroceles, however, if the testis cannot be adequately examined a scrotal ultrasound examination is mandatory. Aspiration of the hydrocele should be avoided because positive cytologic results have been reported in hydroceles associated with testicular tumors.

Other diagnoses to be considered include spermatocele, a cystic mass most commonly found extending from the head of the epididymis; hematocele associated with trauma; granulomatous orchitis, most commonly resulting from tuberculosis and associated with beading of the vas deferens; and varicocele, which is engorgement of the pampiniform plexus of veins in the spermatic cord and should disappear when the patient is in the supine position.

Although most intratesticular masses are malignant, one benign lesion, an epidermoid cyst, may be seen on rare occasions. Usually these cysts are very small benign nodules located just underneath the tunica albuginea; however, on occasion they can be large. The diagnosis is usually made following inguinal orchiectomy; as frozen sections, the larger lesions are often difficult to distinguish from teratoma.