The heritability of larval and juvenile growth in natural and cultured populations of the Manila clam Ruditapes philippinarum was estimated using an unbalanced nested design and an artificial fertilization technique. A total of 33 full-sib families and 10 half-sib families were obtained from the natural population in Shihe (Dalian, Liaoning Province in the north-eastern part of China), whereas 11 half-sib families and 33 full-sib families were generated from the cultured population in Putian (Fujian Province in the south-eastern part of China). The offspring from each family were reared under the same hatchery and nursery conditions. Results from these studies led to estimates indicating a significantly greater influence due to the dam component compared with the sire component for both natural and cultured populations, which was mainly due to maternal effect. We found that the heritability estimates obtained from the intra-group correlation of sire half-sib were precise and unbiased. The narrow-sense heritabilities of shell length for the Manila clam in the natural population (NP) at larval (at the age of 9 days) and juvenile (at the age of 30 days) stages were 0.22 ± 0.11 and 0.39 ± 0.14, respectively, whereas those in the cultured population (CP) were 0.17 ± 0.09 and 0.87 ± 0.24 respectively. The heritabilities of both NP and CP at 3 days were not significantly different from zero, and were −0.03 for NP and −0.14 for CP. These results suggest that selection should be highly effective in Manila clam, and that selecting either a natural or a cultured population for producing faster growing larvae and juveniles should be successful. Selective breeding could thus be used to develop high-quality seed that would facilitate the development of a shorter culture cycle and higher yields.