Background: Staphylococcal scalded skin syndrome (SSSS) and toxic epidermal necrolysis (TEN) both present with acute onset, high morbidity and significant mortality. Rapid diagnosis is therefore of importance. The aim of this study was to investigate and compare the presentation of these diseases using optical coherence tomography (OCT). Methods: Two male patients with bullous diseases, SSSS and TEN, respectively, were photographed digitally, examined using dermoscopy, OCT scanned and subsequently biopsied in the said order. Results: The bullous skin was visualized by OCT showing two distinct images: the SSSS-patient displayed superficial hyporefletive flaccid structures with a split high in the thickened (0.51 mm vs. 0.12 mm) epidermis while the TEN-patient demonstrated a larger hyporeflective ovoid structure with a split right below the thickened epidermis (0.18 mm vs. 0.06 mm). Conclusion: These findings suggest that there is a potential for the application of OCT scanning in the acute phase of SSSS and TEN in order to distinguish them for a faster diagnosis and better management and treatment.