VAS appears as a rapidly growing firm mass in and under the skin. The mass is often quite large when first detected and can become ulcerated or infected. It often contains fluid-filled cavities, probably because of its rapid growth. Diagnosis of VAS is through a biopsy. The biopsy will show the presence of a sarcoma, but information like location and the presence of inflammation or necrosis will increase the suspicion of VAS. It is possible for cats to have a granuloma form after vaccination, so it is important to differentiate between the two before radical surgery is performed. One guideline for biopsy is if a growth is present three months after surgery, if a growth is greater than two centimeters, or if a growth is becoming larger one month after vaccination.

X-rays are taken prior to surgery because about one in five cases of VAS will develop metastasis, usually to the lungs but possibly to the lymph nodes or skin.

New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit type and frequency of vaccinations given to cats. Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats. Feline rhinotracheitis/panleukopenia/calicivirus vaccines should be given as kittens, a year later and then every three years. Also, vaccines should be given in areas making removal of VAS easier, namely: as close as possible to the tip of the right rear paw for rabies, the tip of the left rear paw for feline leukemia (unless combined with rabies), and on the right shoulder—being careful to avoid the midline or interscapular space—for other vaccines (such as FVRCP). There have been no specific associations between development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.