Aim To assess the clustering of behavioral risk factors (BRFs) for chronic noncommunicable diseases and their association with biological factors and cardiorespiratory fitness levels among adolescents in Crete, Greece. Subjects and methods Among 589 adolescents aged 14.0-16.6 years, five BRFs (smoking, physical inactivity, sedentary behavior, alcohol consumption, high body weight) were estimated, and a clustering score of 0, 1, 2 or 3+BRFs was calculated. Biological factors (blood pressure, blood glucose, serum lipids) and cardiorespiratory fitness were also assessed, and their associations with BRFs were examined. Results Physical inactivity was the most prevalent risk factor (48.2 %), whereas smoking was the least prevalent (8.7 %). Approximately 11.4 % of the adolescents displayed none of the five BRFs, while 19.5 % displayed 3+factors (boys: 23.2 %, girls: 16.3 %, p>0.05). High body weight was related to almost all biological factors (p<0.05), while cardiorespiratory fitness was related to all BRFs (p<0.05). Compared to adolescents with no BRFs, adolescents with 3+BRFs had higher mean levels of systolic blood pressure (BP) (122.5 vs. 116.8 mmHg, p = 0.001) and triglycerides (73.5 vs. 58.9 mg/dl, p=0.006), and lower levels of HDL-cholesterol (47.1 vs. 53.5 mg/dl, p<0.001) and cardiorespiratory fitness (2.8 vs. 4.8 stages, p<0.001). Only 10 % of the adolescents with no BRFs had low cardiorespiratory fitness, in contrast to 44.8 % of the adolescents with 3+factors (p<0.001). Conclusion Physical inactivity was the most prevalent individual risk factor, while one-fifth of the Cretan adolescents had an extended clustering of BRFs. Systolic BP, lipid levels and cardiorespiratory fitness were related to BRF clustering. Public health providers should adopt measures to improve these factors when designing health-care programs aimed at adolescents.