Bone marrow involvement (BMI) is a key determinant of treatment strategies and clinical prognosis in classic follicular lymphoma (cFL). The diagnostic performance of baseline positron emission tomography/computed tomography (PET/CT) for identifying BMI remains unclear, and its consistency with bone marrow biopsy (BMB) results varies greatly across studies. Such diagnostic uncertainty hinders accurate clinical risk stratification. This study aimed to assess the diagnostic performance of PET/CT and explore associated diagnostic risk factors.

A total of 176 patients with newly diagnosed classic follicular lymphoma were included. Clinical data, hematological parameters, and PET imaging findings were recorded for all patients and compared with the BMB report. Univariate and multivariate analyses were performed to identify risk factors associated with BMB‐confirmed BMI, and corresponding receiver operating characteristic (ROC) curves were plotted to evaluate their diagnostic efficacy.

Taking BMB as the reference standard for detecting BMI, sensitivity and specificity of PET/CT were 57.9% and 70.0%. PET/CT‐derived BMI (p = 0.023), bulky mass (> 6 cm) (p < 0.001), and spleen involvement (p < 0.001) were identified as independent risk factors for BMB‐confirmed BMI with the diagnostic performance (AUC) as 0.639 (p = 0.002), 0.635 (p = 0.002), and 0.702 (p < 0.001), respectively. Furthermore, the combined diagnostic performance of these three factors reached 0.788 (p < 0.001).

Baseline PET/CT provides critical insights into the assessment of BMI in cFL. For patients with PET/CT images of focal with or without diffuse components, BMB may yield false‐negative results due to sampling limitations. For patients with a diffuse component, the presence of bulky disease and spleen involvement is strongly predictive of BMB‐confirmed BMI. Conversely, the absence of PET/CT‐detected BMI, bulky disease, and splenic involvement suggests a low likelihood of BMB‐confirmed BMI.