Kikuchi-Fujimoto disease (KFD) is a self-limited disease without any need of surgical treatments. Sampling of tissue is the only invasive procedure during the clinical course. However, the standard sampling procedure with accuracy, minimal invasiveness, and esthetic maintenance has not been established yet. In this study, a retrospective review of clinical utility and pathological presentations of the ultrasound-guided core biopsy (USCB) and the open biopsy (OB) in consecutive KFD patients. From 2010 to 2012, 34 consecutive patients were enrolled. USCB was performed in 11 patients, and OB was done in 26 patients. KFD was confirmed in 82% cases by USCB. Similar pathological presentations were found both in the specimens of USCB and OB. In the three patients who had received both USCB and OB, KFD was confirmed by USCB in one case, while two by OB. Sampling errors were found both in USCB and OB. For diagnosing KFD, USCB can serve as the first-line diagnostic tool. OB can be applied only in the failed cases of USCB.