Abstract Patients with Bethesda III/IV thyroid nodules may benefit from molecular testing in order to determine the likelihood of malignancy. The goal is to avoid unnecessary surgery for these often-benign nodules. The decision to acquire samples for molecular testing is typically made after formal cytologic interpretation. This creates anxiety and inconvenience for patients who must return for a repeat biopsy. We explored the impact of routinely collecting “just-in-case” samples from each thyroid nodule. Thus, a minimum of 4 samples were acquired from each nodule: 2 for routine cytologic analysis and 2 for possible genomic sequencing. Nodules subsequently determined to be Bethesda III/IV, were further evaluated by sending the prospectively acquired aspirates for genomic sequencing. Over a 7-month period, there were 69 consecutive patients with ages ranging from 24 to 88 years. There were 16 males and 63 females. Six patients had 2 nodules sampled, yielding total of 75 nodules. Of the 75 nodules, 4 (5.3%) were Bethesda I, 37 (49.3%) Bethesda II, 30 (40%) Bethesda III, 0 (0%) Bethesda IV, 1 (1.3%) Bethesda V, and 3 (4%) Bethesda VI. Of the 30 Bethesda III, 18 (60%) were deemed benign (4% risk of malignancy) by genomic testing. Nine (30%) were deemed 50% or 75% suspicious for malignancy. Two (6.7%) yielded insufficient material for analysis and 1 (3.3%) analysis was canceled because of nonpayment. There were no patient complications. Just-in-case samples prevented call-back of 40% of sampled nodules and thus deemed worthwhile and efficient despite adding an estimated 10 minutes to overall procedure time.