The serum free light chain (sFlc) levels were measured for 122 Chinese patients with newly diagnosed symptomatic multiple myeloma (NDSMM), and κ/λ ratios (rFlc) were calculated. The data were analyzed for the roles of sFlc and rFlc in the diagnosis and prognosis of MM. Abnormal sFlc and/or rFlc were detected in 99.2% of patients, demonstrating that the FLC assay is much more sensitive than the commonly used methods. Baseline sFlc and rFlc successfully predicted the overall survival (OS). The median OS was not reached (NR) versus 23 months for the low sFLC group (sFLC-κ < 180 mg/L or sFLC-λ < 592.5 mg/L) and high sFLC group (sFLC-κ ≥ 180 mg/L or sFLC-λ ≥ 592.5 mg/L) (p = 0.001), and NR versus 21 months for the low rFLC group (0.04 ≤ rFLC ≤ 25) and high rFLC group (p < 0.001), respectively. Interestingly, the significant differences in OS between the low and high rFLC groups were not changed by bortezomib chemotherapy. In addition, patients were further stratified by three novel poor-prognosis factors (β(2)-microglobulin [β2-MG] > 3.5 mg/L, albumin [ALB] < 35 g/L, rFLC > 25 or rFLC < 0.04) that were developed from combination of the rFlc with the International Staging System (ISS): the low risk group (no factor), the low-intermediate risk group (one factor), the high-intermediate risk group (two factors) and the high risk group (three factors). The median OS for those groups was NR, NR, 24 months and 13 months, respectively (p < 0.05). In conclusion, the sFLC assay was highly sensitive in the diagnosis of MM in Chinese patients. The prognostic potential of the ISS may be improved with the addition of rFLC.