Objective: Cancer-IgG is a newly-discovered molecule, mainly derived from epithelial carcinoma cells and is significantly correlated with differentiation, metastasis, local invasion, and poor prognosis of many cancers. In our previous study we detected IgG expression in oral epithelial carcinoma, including salivary adenoid cystic carcinoma (SACC), using an IgG-specific commercial antibody. Here, we explored the correlation between cancer-IgG and clinicopathological features of SACC. Design: A total of 68 human SACC tissue specimens and 2 siRNAs were used to analyze the correlation between cancer-IgG and extra domain A (EDA(+))-containing fibronectin using the cancer-IgG-specific monoclonal antibody, RP215. Results: We found an unexpected correlation between cancer-IgG and EDA(+) fibronectin, both of which showed aberrant expression in SACC tissue samples. Both were highly expressed in SACC with nerve invasion. In our previous study, EDA(+) fibronectin overexpression in SACC cells decreased N-cadherin expression. In the present study, we used SACC-83 cells, wherein EDA(+) fibronectin is overexpressed and cancer-IgG is knocked down. EDA(+) fibronectin expression was reduced with cancer-IgG knockdown, while cancer-IgG expression did not affect EDA(+) fibronectin overexpression. Furthermore, knockdown of non-B cell-derived IgG in SACC cells decreased cellular motility (P < 0.05) as well as increased E-cadherin and alpha-smooth muscle actin levels. Conclusion: The results suggest that cancer IgG potentially regulates EDA(+) fibronectin, expression, thereby suggesting possible new therapeutic approaches for SACC.