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Advancements in personalized medicine have increased the demand for quantity and preservation of tissue architecture of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples. These demands may be addressed by the SonoTip TopGain ® needle, which has a 3-point crown-cut design that contrasts with the standard single bevel design of the ViziShot 2 ® . The objective was to compare the SonoTip TopGain ® and ViziShot 2 ® needles by considering biopsy sample characteristics, diagnostic accuracy, and patient safety. The primary endpoint of the study was the number of high-power fields (HPFs) in the center of the formalin-fixed paraffin-embedded cell block per sample. The lymph node with the highest probability for malignant infiltration based on size and sonographic appearance was chosen as the target lymph node for 20 patients. The same lymph node in each patient was sampled using both the ViziShot 2 ® and SonoTip TopGain ® needles. The samples were measured, sliced, and analyzed by a pathologist. Sixteen patients were biopsied with both needles. Four patients could not be biopsied with the SonoTip TopGain ® needle since it could not penetrate cartilage or be repositioned to bypass cartilage. HPFs and sample dimensions were significantly greater in the patients where sampling with the SonoTip TopGain ® needle was possible ( p = 0.007 and p = 0.005, respectively). Diagnostic accuracy and safety profiles were comparable. Significantly more material can be sampled using the SonoTip TopGain ® needle when cartilage penetration can be avoided. This improves the yield for molecular workup in the era of personalized medicine.