The U.S. military has recently re-instituted smallpox vaccination for some service members. Routine smallpox vaccination in the U.S. was halted in 1972 and many physicians are not familiar with complications of the vaccine.

We present a case report of a 21 year-old military reservist who received the smallpox vaccine. Subsequent evaluation for leg pain showed a tumor of the distal femur and he was diagnosed with osteosarcoma 2 weeks after vaccination.

The recent smallpox vaccination was recognized, consequently, chemotherapy was deferred until the scab at the vaccine site fell off 4 weeks after vaccination. Surgery eventually showed 100% necrosis of the tumor and the patient did not develop progressive vaccinia or other vaccine complications.

Immunosuppression is a contraindication for the smallpox vaccine because of the risk for progressive vaccinia. Physicians must screen carefully for immunosuppressed states prior to vaccination, especially given the increased use of immunosuppressive therapies compared with 30 years ago, and the prevalence of HIV/AIDS. Conversely, immunosuppressive therapies should not be initiated immediately after smallpox vaccination. This case demonstrates that chemotherapy was given safely and efficaciously to our patient after his scab fell off, representing the end of active vaccinia infection. We hope this report may provide guidance to others in a similar, difficult situation in which urgent immunosuppressive therapy is needed in the setting of recent, coincidental smallpox vaccination.