<b><i>Introduction:</i></b> Thyroid cytology is a widely accepted tool in the clinical triaging of nodular lesions. Cell blocks (CBs) can help in the diagnosis of atypical lesions, namely, thyroid Bethesda category of Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). <b><i>Methods:</i></b> In a series of 224 AUS/FLUS thyroid samples with CB, we studied CB cellularity and feasibility of 3 immunohistochemical markers (cytokeratin 19 [CK19], HBME-1, and galectin-3) apart and in combination. <b><i>Results:</i></b> The CBs were non-diagnostic in 34 cases. Twenty-four CBs contained &#x3c;10 cells, 45 CBs 10–50 cells, and 121 CBs &#x3e;50 cells. Notably, more cellularity was found in CBs performed by plasma-thrombin and in-house techniques (<i>p</i> &#x3c; 0.001). The diagnostic accuracy to detect malignancy was 65.1% for CK19, 72.1% for HBME-1, and 70.3% for galectin-3. <b><i>Conclusion:</i></b> In conclusion, CB cellularity is essential for successful immunohistochemistry application and further diagnostic workup of AUS/FLUS cases.

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