Dyspnea in a HIV patient often warrants an extensive workup. The most common etiology of this presentation is likely due to an infectious etiology. However, with the introduction of antiretroviral treatment, non-AIDS-defining illness including malignancies are increasingly being reported. We report the case of a 46-year-old African American female, nonsmoker who presented with dyspnea and found to have pericardial effusion. In patients with HIV presenting with dyspnea, pericardial effusion should be considered among the differential diagnosis, more so in patients in whom infectious etiologies have been ruled out. Further workup, including imaging and biopsy, revealed that our patient had metastatic lung adenocarcinoma. The introduction of antiretroviral treatment has significantly reduced mortality for those with AIDS from AIDS-defining illness and malignancies. However, the incidence of non-AIDS-defining malignancies like lung adenocarcinoma (most common non-AIDS-defining malignancy) is being increasingly reported. Lung adenocarcinoma often presents at a younger age in patients with HIV than the general population. Smoking rates are higher in patients with HIV and may be a contributing factor to the early onset of lung cancer; however, other factors such as long-term medications and immunomodulation in HIV may also play a role. Prognosis is also worse for HIV-positive patients having lung cancer compared with those who are HIV negative, even at a similar stage of cancer.