Small and non-small cell lung cancer present in a variety of radiologic and clinical patterns, and have been linked to smoking. Primary adenocarcinoma of the lung has been increasingly recognized in females and nonsmokers, often presenting a diagnostic challenge. In the absence of smoking history, these radiographic patterns may be initially misdiagnosed as an infectious or inflammatory condition, often delaying the diagnosis of malignancy. We report two cases of female patients with relatively short or no smoking history presenting with diffuse pulmonary infiltrates not typically seen in primary lung cancer, which created a diagnostic challenge, ultimately diagnosed as primary lung adenocarcinoma. Each case had different subtype patterns of adenocarcinoma. The first case described adenocarcinoma of mostly acinar pattern; while the second case was noted to have adenocarcinoma of micropapillary pattern. Given lung adenocarcinoma's nonspecific presentation, which may mimic infectious and diffuse interstitial lung disease, the above cases highlight the importance of entertaining lung adenocarcinoma as part of the differential diagnosis of such presentations.