INTRODUCTION: This study aimed to assess the feasibility of implementing the Idylla system, an ultra-rapid, cartridge-based assay, as an extension of rapid on-site evaluation (ROSE) in cytology. The authors conducted a pilot validation study on specimens from non-small cell lung carcinoma, thyroid carcinoma, and melanoma, evaluating four assays designed to detect alterations in KRAS, EGFR, BRAF, gene fusions, and expression imbalances in ALK, ROS1, RET, NTRK1/2/3, and MET exon 14 skipping transcripts. They investigated the feasibility of providing accurate biomarker molecular testing results in a cytopathology laboratory within hours of specimen collection. METHODS: The authors evaluated the performance characteristics and turn-around-time of the Idylla system by testing a total of 144 cartridge assays across various specimen types, including fine-needle aspirate smears, formalin-fixed paraffin-embedded (FFPE) cell blocks, small tissue biopsy FFPE blocks, and control cell line FFPE scrolls. RESULTS: The average time from specimen input to results output was 2-3 hours. Accuracy across the four cartridge types was: KRAS assay: 100%, EGFR assay: 94%, BRAF assay: 100%, and GeneFusion assay: 94%. Analytical sensitivity ranged from 1% to 5% variant allele frequency for all assays. Inter-assay precision and analytical specificity were both 100%. CONCLUSION: Using the Idylla system, actionable genetic alterations can be reliably detected within 2-3 hours from cytology and small biopsy samples with minimal input requirements. The findings of this study demonstrate the feasibility of incorporating same-day molecular testing as part of ROSE procedures in the cytopathology laboratory, ultimately shortening the time from procedure to personalized treatment for cancer patients.