Introduction. Skin failure may be both visually similar in appearance and can occur concomitant to a pressure injury, but it has a fundamentally different etiology. To date, no validated assessment tools or clinical indicators are available that can help definitively distinguish skin failure from a pressure injury. Objective. The Skin Failure Clinical Indicator Scale (SFCIS), a proposed tool that uses readily available variables to assist in more definitively identifying skin failure, was developed and assessed. Methods. A retrospective case-control study was conducted among acute care hospital patients who experienced acute skin breakdown before death. Data were extracted from the electronic medical records of deceased acute care patients who experienced acute skin breakdown prior to death between January 1, 2017, and March 1, 2019, in 2 US hospitals. Using ICD-10 coding, patients were separated into 2 groups depending on if the skin breakdown occurred at locations typical for pressure injury formation or atypical (non-pressure) locations. Patient diagnostic and clinical data were compared between the 2 groups. Univariate and multivariate data analyses were performed via backward stepwise logistic regression in order to identify significant predictors of skin failure; regression coefficients were converted into integers in order to create a tool that could assist in probable identification of skin failure. Results. Of the 52 patients included in this study, 16 experienced skin breakdown at locations typical for pressure injury and 36 had skin breakdown in atypical locations, which was assumed to be indicative of skin failure. Factors found to help distinguish between skin failure and pressure injury included a serum albumin level less than 3.5 mg/dL (P = .07), impaired blood flow (P = .05), presence of sepsis/multiorgan dysfunction syndrome (P = .001), vasopressor/inotrope use (P < .001), and mechanical ventilation (P = .06), which ultimately correctly identified 83.7% as cases of probable skin failure. Conclusions. This scale may provide a means to correctly recognize and diagnose skin failure, initiate appropriate interventions, and decrease potential reimbursement penalties to facilities. Further testing will be necessary in order to validate the specificity and selectivity of this instrument.