Background <p>Severe misdiagnosis of scabies can result in prolonged symptoms, inappropriate use of immunosuppressive therapy, secondary infections, and transmission within an institution. Hospitalized patients frequently present with atypical morphology or distribution, leading to uncertainty in diagnosis.</p> Objective <p>This study aimed to identify clinical characteristics associated with severe misdiagnosis of scabies using a study-defined pragmatic grading system developed to capture diagnostic delay, inappropriate treatment exposure, and adverse clinical consequences.</p> Methods <p>We performed a retrospective review of 41 patients admitted to the hospital and subsequently confirmed to have scabies. Because no validated grading system currently exists for the severity of scabies misdiagnosis, we applied a study-defined, pragmatic four-level classification (Levels 0–3) based on diagnostic delay, inappropriate treatment exposure, and clinical consequences. Levels 2 and 3 were defined as severe misdiagnosis. Univariate logistic regression was performed to assess factors associated with severe misdiagnosis, whereas univariate ordinal logistic regression (proportional odds model) was performed to explore associations across the entire severity grading system.</p> Results <p>Severe misdiagnosis was identified in 10 of 41 patients (24.4%). Interdigital involvement was associated with lower odds of severe misdiagnosis (OR 0.048, 95% CI 0.008–0.297; <i>P</i> = 0.001), whereas generalized involvement was associated with higher odds of severe misdiagnosis (OR 7.27, 95% CI 1.31–40.42; <i>P</i> = 0.023). Ordinal regression showed directionally consistent findings: generalized involvement was associated with higher misdiagnosis grades (common OR 14.74; <i>P</i> = 0.002), whereas interdigital involvement was associated with lower misdiagnosis grades (common OR 0.106; <i>P</i> = 0.003). Age showed a non-significant trend toward higher misdiagnosis severity. Routine laboratory tests showed limited discriminatory value.</p> Conclusions <p>In this retrospective hospital-based cohort, absence of classical interdigital involvement and generalized distribution were associated with higher grades of scabies misdiagnosis in univariate exploratory analyses. Bullous morphology also showed a non-significant trend toward higher misdiagnosis severity. These findings are hypothesis-generating and most applicable to similar hospitalized populations. Targeted examination of classic sites or empirical treatment when a diagnosis is suspected remains crucial, especially in cases of widespread or atypical presentations. Larger prospective studies are needed to validate the proposed study-defined grading system and to determine whether these clinical patterns can reliably guide diagnostic decision-making.</p>