Recent studies indicate that certain key molecules that are vital for various developmental processes, such as Wnt, Shh, and Notch, cause cancer when dysregulated. PTEN, a tumor suppressor that antagonizes the PI3 kinase pathway, is the newest one on the list. The biological function of PTEN is evolutionarily conserved from C. elegans to humans, and the PTEN-controlled signaling pathway regulates cellular processes crucial for normal development, including cell proliferation, soma growth, cell death, and cell migration. In this review, we will focus on the function of PTEN in murine development and its role in regulating stem cell self-renewal and proliferation. We will summarize the organomegaly phenotypes associated with Pten tissue-specific deletion and discuss how PTEN controls organ size, a fundamental aspect of development. Last, we will review the role of PTEN in hormone-dependent, adult-onset mammary and prostate gland development.