There are four well-established risk factors for testis cancer:

• Cryptorchidism (an undescended testicle).
• Family history.
• Personal history.
• Intratubular germ cell neoplasia (ITGCN).

The most common risk factor for testis cancer is a history of cryptorchidism, otherwise known as an undescended testicle. Normally in the developing male fetus, the testicles form near the kidneys in the abdomen (belly). About the eighth month of pregnancy, the testicles descend, exit the body and settle in the scrotum. About 3% of boys have one or both testicles that fail to make it into the scrotum. Testicles can settle in the abdomen or in the inguinal canal or groin (where the testicle exits the body wall and enters the scrotum). Most of the time, an undescended testicle will move down and settle into the scrotum within the first year of life. Sometimes surgery is required to bring down and fix the testicle to the scrotum — this surgery is called an orchiopexy.

Boys with a history of cryptorchidism have an increased risk of testis cancer. The risk of cancer is not directly related to the fact that the testicle does not descend, but it is believed that the abnormality in descent likely indicates an abnormality in the testicle that makes cancer more likely. This belief is based on the following observations: The cancer usually develops in the undescended testicle (four- to sixfold increased risk of cancer), but the risk of cancer is also higher in the normal testicle (less than twofold increased risk). In addition, generally the higher the testicle, the higher the risk of testis cancer — intra-abdominal testis have a much higher risk of cancer than those in the inguinal canal. Early surgery (orchiopexy) reduces the risk of testis cancer (two- to threefold risk if the surgery is performed prior to puberty) but does not erase the chance for that boy to develop cancer later in life.

A family history of testicular cancer is another common risk factor, with an eight- to twelvefold risk if a man has a brother with testis cancer and a two- to fourfold risk if his father has testis cancer. While there is not a specific gene linked to testicular cancer, the disease is highly heritable and can be passed from generation to generation. In addition, the average age at diagnosis is two to three years younger than the general population if a first-degree relative has testicular cancer. However, it should be remembered that testis cancer is rare, and it is therefore rare for this disease to run in families.

Men with a personal history of testicular cancer have the highest risk of developing another cancer. Fortunately, only 2% of men will develop cancer in both testicles, but that risk is twelvefold higher than men without testis cancer. In addition, men who develop testis cancer in their 20s or earlier, men with seminoma and men with ITGCN have a higher risk of developing a second testis cancer.

Most testis cancer arises from the precursor lesion known as GCNIS (or germ cell neoplasia is situ, formerly known as carcinoma in situ, CIS or ITGCN). GCNIS is present adjacent to testis cancer in 80–90% of patients. For men in whom GCNIS is found for other reasons, the risk of subsequent testis cancer is 50% at five years and 70% at seven years. Therefore, GCNIS is the last well-known risk factor for testis cancer.

Microlithiasis, or small calcifications (stones) in the testicle found on ultrasound, was once believed to be a risk factor for testicular cancer. Microlithiasis is not a risk factor for testicular cancer for most men; however, if one of the other risk factors (above) exists, microlithiasis may indicate a higher risk of cancer and warrants monthly testicular self-examination and routine follow-up with a physician.

Tobacco smoking, bicycle riding, obesity and height are not risk factors for testicular cancer.