Introduction: Endoscopic ultrasound (EUS)-guided fine needle aspiration/biopsy (EUS-FNA/FNB) to obtain cytological aspirates and histological core samples have been the standard of care for diagnosis of solid or cystic lesions in or nearby upper and lower gastrointestinal tract. Due to lack of standardization of tissue processing, it is unclear as to whether core sample should be sent only for histology (in formalin), or for cytology (in cytolyte) or for both. The aim of this study is to investigate the concordance rates observed between cytology compared with histology on samples obtained using EUS-FNA/FNB. Methods: Out of 226 patients who underwent EUS-FNA/FNB using a 22-gauge needle between October 2017 and February 2019 by a single therapeutic endoscopist, 46 patients were selected for final evaluation, in whom equal number of passes were sent for both histology and cytology. Patient's demographics, medical history, imaging (prior computed tomography /magnetic resonance imaging), indication for EUS, EUS findings, and cytology/histology results were analyzed. The main outcome measures were diagnostic accuracy for malignancy and concordance between cytology and histology. Results: In 46 patients, the acquired core samples were placed alternately in cytolyte (for cytology) and formalin (for histology), with equal number of passes into each, to best achieve proportionate amount of samples. These samples were obtained from solid masses in 78% (36/46), lymph nodes in 13% (6/46) and from cystic lesions in 8.6% (4/46) of cases. Analysis was remarkable for diagnosis consistency in 42 out of 46 samples (91.3%). Cytology and histology were found to be discordant in four cases. Cytology was reported inconclusive in 1 and negative in 3 of these cases, but definitive diagnosis was achieved with histology, which was positive for neoplasm in all 4 cases. These samples were obtained from two pancreatic masses, one gastric subepithelial lesion, and one lymph node; and histology confirmed pancreatic adenocarcinoma, gastrointestinal stromal tumor, and follicular lymphoma, respectively. Discussion: Our study observed an 8% diagnostic discordance between cytology and histology on core samples obtained using EUS-FNB, when it was sent for both cytology and histology in equal proportions. Diagnostic yield of histology was noted to be superior to cytology, especially in cases with cytological diagnostic uncertainty. Further large, randomized and prospective studies are needed to ascertain a best and universally acceptable practice to make the diagnostic process more efficient, accurate, and cost-effective.