A patient complaining of severe pain in the right submandibular area showed a huge sialolith in radiogram. During the operation, the submandibular gland was much indurated, and large amount of pus was discharged out at an incision of the salivary gland. The removed salivary gland contained a huge sialolith in the major excretory duct of submandibular gland, which had an intact grayish-white surface in ovoid shape. In the histological examination its excretory ducts were extensively dilated without extravasation of saliva, and the involved salivary gland was almost destroyed by the granulomatous r eaction. Most of a cinar cells were d isappeared and r eplaced by ductal cells filled with exudative materials. The microsections of sialolith showed typical laminar structures of calcification containing amorphous basophilic material in the center, in which a lot of Gram positive and Gram negative microorganisms were found. In the center of sialolith numerous microorganisms were admixed with mucinous materials which were strongly positive for the antibody of mucin-1, and formed multiple colonies. In the periphery of the bacterial colonies proline rich proteins (PRPs) were condensely localized, and followed by the consistent positive reaction of transglutaminase 4 (TGase-4). These data suggest that the sialolith of this study is formed from the primary nidus of bacterial colony aggregated with salivary mucin-1 and PRPs by the crosslinking reaction of TGase-4.