Two previously healthy men who presented with hypotension, constitutional symptoms, and targetoid and discrete spotty erythematous plaques were diagnosed with toxic shock syndrome based on histopathological findings. Specifically, their biopsies revealed necrotic keratinocytes, neutrophils in the epidermis, and neutrophils surrounding dilated superficial vessels. In one case, the diagnosis of toxic shock syndrome was confirmed with rising titers to toxic shock syndrome toxin-1. Both patients recovered with supportive care and clindamycin administration. We suggest that patients with fever, hypotension, constitutional symptoms and rash should be started on clindamycin and have a skin biopsy as part of their initial evaluation. An understanding that toxic shock syndrome can strike anyone has manifold dermatological manifestations and defined histopathological findings is important for its early diagnosis and effective treatment.