OBJECTIVE: To obtain definitive cancer diagnosis for suspicious lesions, accurate needle deployment and adequate tissue sampling in needle biopsy are essential. However, the single-bevel needles in current biopsy devices often induce deflection during insertion, potentially causing lesion missampling/undersampling and cancer misdiagnosis. This study aims to reveal the biopsy needle design criteria enabling both low deflection and adequate tissue sampling. METHODS: A novel model capable of predicting needle deflection and tissue deformation was first established to understand needle-tissue interaction with different needle tip geometries. Experiments of needle deflection and ex-vivo tissue biopsy were conducted for model validation. RESULTS: The developed model showed a reasonably good prediction on the correlation of needle tip type vs. the resultant needle deflection and tissue sampling length. A new multi-bevel needle with the tissue separation point below the needle groove face has demonstrated to be an effective design with an 87% reduction in deflection magnitude and equivalently long tissue sampling length compared to the current single-bevel needle. CONCLUSION: This study has revealed two critical design criteria for biopsy needles: 1) multiple bevel faces at the needle tip can generate forces to balance bending moments during insertion to enable a low needle deflection and 2) the tissue separation point should be below the needle groove face to ensure long tissue sampling length. SIGNIFICANCE: The developed methodologies and findings in this study serve as proof-of-concept and can be utilized to investigate various biopsy procedures to improve cancer diagnostic accuracy as well as other procedures requiring accurate needle insertion.