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13 reviewsSUMMARYRapid identification and accurate diagnosis are critical for individuals with acute leukemia (AL). Here, we propose a combined deep learning and surface-enhanced Raman scattering (DL-SERS) classification strategy to achieve rapid and sensitive identification of AL with various subtypes and genetic abnormalities. More than 390 of cerebrospinal fluid (CSF) samples are collected as targets, encompassing healthy control, AL patients, and individuals with other diseases. Sensitive SERS detection could be achieved within 5 min, using only 0.5 μL volume of CSF. Through integrated feature fusion (1D spectra and 2D image) with a transformer model, the classification method is developed to screen and diagnose AL patients, demonstrating exceptional classification performances of accuracy, sensitivity, specificity, or reliability. Also, this approach demonstrates remarkable versatility and could be extended to the classifications of meningitis diseases. The sensitive DL-SERS classification platform has the potential to be a powerful auxiliary in vitro diagnostic tool.