Aim of the work to study the relationship between collagen triple helix repeat containing 1 (CTHRC1) protein serum levels and disease activity, patients’ well-being, as well as ultrasonographic and radiological scores in patients with rheumatoid arthritis (RA). Patients and methods The work included 70 RA patients and 70 age and gender matched controls. The disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Modified Larsen's score was used to score the hands and feet digital radiographs and musculoskeletal ultrasound (MSUS) examination using ultrasound-7 score was carried out. Serum CTHRC1 levels were measured by ELISA. Results Patients were 62 females and 8 males (F: M 7.8:1), their mean age was 42.2 ± 17.7 years and median disease duration 15 years. The median CTHRC1 serum levels were significantly higher in patients (453 ng/dl; 158–688 ng/dl) than control (99 ng/dl; 67–179 ng/dl) (p < 0.001). CTHRC1 was significantly increased in those with high activity (p < 0.001).CTHRC1 levels significantly correlated with DAS28 (r = 0.87,p < 0.001), CRP (r = 0.43,p < 0.001) and total ultrasound-7 score (r = 0.27,p = 0.03). Only total US7 score (p = 0.003) and CTHRC1 (p < 0.001) were significant predictors of activity. Serum CTHRC1 could significantly differentiate between patients and controls at cut off 179 ng/ml; sensitivity 95.7 % and specificity 100 % (p < 0.001) and between patients active and in remission at cut off 324 ng/ml; sensitivity 92.2 % and specificity 94.7 % (p < 0.001). Conclusions Patients with RA have significantly elevated serum levels of CTHRC1. In the process of structural bone ultrasonographic abnormalities as well as disease activity in RA patients, elevated CTHRC1 levels play a key role.