The diagnosis of acute infection with human immunodeficiency virus (HIV) presents a challenge for the primary care provider. We present a case of early HIV infection and discuss the limitations of the currently established diagnostic algorithm for HIV infection. We conclude that alternative diagnostic testing for human immunodeficiency virus type 1 (HIV-1) RNA is warranted in certain clinical settings. Appropriate, early diagnosis of HIV infection may improve the patient's outcome and provide additional public health benefits by reducing transmission of disease.