Both endometriosis and adenomyosis are common benign gynecological diseases. This study aimed to find the novel noninvasive, biochemical diagnostic markers for detection of endometriosis and adenomyosis, and evaluate the correlation of these two diseases at the protein level. Serum samples from patients with endometriosis or adenomyosis were compared with control groups to detect specific serum biomarkers and to explore the different protein fingerprint of endometriosis and adenomyosis using MALDI-TOF-MS. There were 13 protein peaks abnormally expressed in endometriosis as well as twelve in adenomyosis compared with control groups (P < 0.05). And five-peak mass was found downregulated significantly both in the women with endometriosis and adenomyosis. The common diagnostic model of endometriosis and adenomyosis we set up had a lower sensitivity and specificity than the separate diagnostic model of these two diseases. MALDI-TOF-MS technology plays an important role in screening the diagnostic biomarkers of endometriosis and adenomyosis. And our study found the correlation between endometriosis and adenomyosis in protein fingerprint and it is hard to separate the endometriosis from adenomyosis with the serum biomarkers.