Antibody screening alone may fail to detect human immunodeficiency virus (HIV) in recently infected individuals. By U.S. Army regulation, HIV-infected soldiers are not permitted to deploy to areas of conflict, including Iraq and Afghanistan. We report here the first case of acute HIV infection (AHI) in a soldier in a combat area of operation detected by an enhanced U.S. Army HIV testing algorithm and discuss features of the tests which aided in clinical diagnosis. We tested the sample from the AHI case with a third generation HIV-1/HIV-2 plus O enzyme immunoassay, HIV-1 Western Blot, and a qualitative HIV-1 ribonucleic acid molecular diagnostic assay. Risk factors for HIV acquisition were elicited in an epidemiologic interview. Evaluation of the blood sample for AHI indicated an inconclusive serologic profile and a reactive HIV-1 ribonucleic acid result. The main risk factor for acquisition reported was unprotected sexual intercourse with casual strangers in the U.S. while on leave during deployment. The clinical diagnosis of AHI in a combat area of operation is important. Diagnosis of HIV is key to preventing adverse effects to the infected soldier from deployment stressors of deployment and further transmission via parenteral or sexual exposures.