BACKGROUND The management of invasive fungal infection (IFI) is challenging in immunocompromised patients who do not fully satisfy the EORTC/MSG diagnostic criteria of proven or probable IFI. Our study assessed caspofungin efficacy in 582 Chinese patients with hematological malignancies exhibiting unclassified signs or symptoms of IFI. MATERIAL AND METHODS This retrospective study included caspofungin treatment outcomes of an unclassified group A (n=401) of patients without microbiological or biomarker results and group B (n=181) patients with positive microbiological or biomarker results. Factors that correlated with clinical outcomes were determined using univariate and multivariate analyses. RESULTS Cough (41.8%), expectoration (29.6%), and chest tightness (14.6%) were the most common clinical features, and changes in CT images (88.1%) were more frequently detected than in X-ray images (19.6%) in all patients. Favorable response rates for caspofungin as first-line treatment were 58.2% for group A and 56.3% for group B. Eastern Cooperative Oncology Group (ECOG) score, cardiovascular disease, hemoptysis, and absolute neutrophil count (ANC) <1000/mm³ before antifungal treatment without recovery were associated with unfavorable clinical outcome (P<0.05 for all). Cough and ANC recovery >1000/mm3 were significantly associated with favorable (complete or partial resolution) outcome. CONCLUSIONS Caspofungin was effective for treating unclassified IFIs of immunocompromised patients. Cardiovascular disease, ECOG score, cough, and/or hemoptysis, as well as ANC count, represent a potential index for estimating response of unclassified IFI patients to caspofungin treatments.