Objective: Squash preparation (SP) is a rapid technique for the intraoperative assessment of brain lesions. Only a few studies have employed touch preparation (TP) cytology and Diff-QuikTM (DQ) staining in conjunction with SP. Our study aimed to assess the diagnostic efficacy of SP of brain lesions at our institution, ascertain the additional effect of TP and DQ staining, examine factors affecting the sensitivity and specificity of our methods, and compare our findings with those of previous investigations. Study Design: Our database was searched for all SP/TP of brain lesions examined from January 1996 to December 2016. Results: During this 20-year study period, our search revealed 400 brain lesions diagnosed by SP/TP cytology. There were 338 (84.5%) neoplasms and 62 (15.5%) nonneoplastic lesions. The most common neoplasms were glioblastoma multiforme (24.6%), metastatic cancer (18.3%), meningioma (16.9%), astrocytoma (11.5%), lymphoma (8.3%), oligoastrocytoma (3.3%), and pituitary adenoma (3.3%). There was discordance between the SP/TP and histological diagnoses in 19/338 (5.6%) cases, i.e., 12 misclassifications of tumor subtype and 7 sampling errors. No false-positive cases were detected. Conclusion: Brain SP/TP stained with H+E/DQ demonstrated high sensitivity (97.9%), specificity (100%), and overall diagnostic accuracy (95.3%). The combined methods, in particular, aided in the diagnosis of brain tumors prone to smearing artifacts and certain metastatic malignancies.