Spontaneous pneumomediastinum is an uncommon, self-limiting condition resulting from alveolar rupture in young adults. Because of the ambiguous presentation and the general lack of awareness of this condition, its diagnosis is often delayed, missed, or confused with spontaneous esophageal perforation. We report our experience of treating six patients who were referred to our unit with vomiting-induced pneumomediastinum, subcutaneous emphysema, and an initial diagnosis of spontaneous esophageal perforation. Ultimately, we diagnosed spontaneous pneumomediastinum in all six patients, who recovered uneventfully without any surgical intervention. We review the literature with particular emphasis on differentiating spontaneous pneumomediastinum from spontaneous esophageal perforation.