Studies on the serum biomarkers of granulomatous inflammation and pulmonary interstitial disease in intrathoracic sarcoidosis have shown conflicting results. We postulated that differences in the concentrations of serum biomarkers can be explained by the heterogenous patterns of sarcoidosis seen on thoracic HRCT. Serum biomarker levels in 79 consecutive patients, newly diagnosed with intrathoracic sarcoidosis, were compared to our control group of 56 healthy blood donors. An analysis was performed with respect to HRCT characteristics (the presence of lymph node enlargement, perilymphatic or peribronchovascular infiltrates, ground-glass lesions, or fibrosis), CXR, and disease extent. Serum levels of CXCL9, CXCL10, CTO, and CCL18 were statistically significantly increased in all patients compared to controls. Serum levels of CA15.3 were statistically significantly increased in all patients with parenchymal involvement. SAA was increased in patients with ground-glass lesions while SP-D levels were statistically significantly increased in patients with lung fibrosis. Only SP-D and CA15.3 showed a significant correlation to interstitial disease extent. In conclusion, we found that sarcoidosis patients with different HRCT patterns of intrathoracic sarcoidosis have underlying biochemical differences in their serum biomarkers transcending Scadding stages. The stratification of patients based on both radiologic and biochemical characteristics could enable more homogenous patient selection for further prognostic studies.