Large biopsy needles (18 and 19 gauge) have been reported to yield high-quality tissue cores for reliable histologic diagnosis. In our institution, image-directed percutaneous biopsy specimens obtained with these needles are processed routinely for simultaneous cytologic and histologic analysis. For the present study, we reviewed our experience with 82 such biopsies of the thoracoabdominal region. We examined the value of cytologic analysis as a supplement to histologic analysis of such biopsies in terms of diagnostic yield and sensitivity for detecting malignancy. Among the 82 specimens, material was adequate for histologic diagnoses in 70 (85%) and for cytologic diagnosis in 63 (77%). Combining the histologic and cytologic results increased the diagnostic yield to 93% (76 of 82 specimens). Forty-eight lesions were diagnosed as malignant by either one or both means of analysis. While histologic analysis produced 44 of the 48 positive results (92%), cytologic analysis produced 33 (66%) (P < .05, McNemar's test). Because tissue fragments were selected preferentially for histologic processing, histologic evaluation was more valuable than cytologic evaluation in achieving definitive diagnoses of malignancy. In spite of this bias in preparation technique, malignancy was diagnosed by cytologic analysis alone in 4 of the 48 positive cases (8%). We conclude that the combined approach of histologic and cytologic examination of large-gauge core needle biopsy specimens maximizes the diagnostic yield and sensitivity for detecting malignancy.