Purpose <p>Ameloblastoma (AM) is a clinically significant odontogenic tumour known for its local invasive and high post-treatment recurrence risk. Despite advancements in surgical techniques, predicting recurrence remains challenging. The role of immunomarkers in predicting recurrence of ameloblastoma remains non-conclusive. The aim of this study is to investigate the predictability of recurrence using selected immune markers.</p> Methods <p>42 AM samples comprising 16 non-recurrent AM (AMNR), 13 primary tumour of recurrent AM (PAMR), and 13 recurrent AM from the same patient as PAMR (RAM) were immunohistochemically examined for the expression of interleukin 1-alpha (IL-1α), interleukin 6 (IL-6) and CD 10. Immunoreactive scoring (IRS) was used to assess the expression levels. The expression levels were further analyzed for the correlation with demographic and clinicopathological parameters of interest.</p> Results <p>The three markers were heterogeneously expressed in the ameloblastoma samples (IL-1α = 97.6%; IL-6 = 97.6% and CD 10 = 90.5%). Major findings were the upregulation of IL-6 (RAM &gt; PAMR &gt; AMNR) in RAM, while IL-1α and CD 10 scored higher in AMNR (AMNR &gt; PAMR &gt; RAM). Further correlation with clinicopathological parameters showed significant association between IL-1α expression with histopathological variants in AMNR (<i>p</i> = 0.03) and PAMR (<i>p</i> = 0.002). IL-6 expression was significantly correlated with tumour locality in AMNR (<i>p</i> = 0.01), and CD 10 showed significant correlation with tumour locality in PAMR (<i>p</i> = 0.02) and subsites of tumour locality in PAMR (<i>p</i> = 0.005) and RAM (<i>p</i> = 0.002).</p> Conclusion <p>The upregulation of IL-6 in recurrent ameloblastoma may predict its potential for recurrence. However, this interpretation should be considered tentative due to the inherent limitations of the study. Immunoexpression of IL-1α and CD 10 requires further investigation to elucidate their roles in tumourigenesis and invasiveness of ameloblastoma.</p>