Spontaneous perforation of the esophagus (Boerhaave syndrome) is an emergency that requires early diagnosis if death or serious prolonged illness is to be averted. The cases of three patients with spontaneous esophageal perforation simulating other primary diagnoses are described. The respective referral diagnoses were pericarditis, lung abscess, and pancreatitis. Each case was characterized by severe illness, and by delay in diagnosis despite multiple consultations. Two patients died. The literature is reviewed and the causes of delay in diagnosis are analyzed. More than 40 years after the first report of successful surgical repair, spontaneous esophageal perforation is insufficiently considered in diagnostic hypotheses, yet may be confirmed or excluded by simple methods. All clinicians need to be alert to this lethal disease, and to be aware of its frequent atypical presentations.